Simian immunodeficiency virus (SIV) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. However, very little is known about the pathogenesis of SIV or simian human immunodeficiency virus (SHIV) in cynomolgus macaques from different Asian countries. In the present study, we analysed the infectivity and pathogenicity of CCR5-tropic SIVmac and those of dual-tropic SHIV89.6P inoculated into cynomolgus macaques in Indonesian, Malaysian or Philippine origin. The plasma viral loads in macaques infected with either SIVmac239 or SHIV89.6P were maintained at high levels. CD4+ T cell levels in macaques infected with SIVmac239 gradually decreased. All of the macaques infected with SHIV89.6P showed greatly reduced CD4+ T-cell numbers within 6 weeks of infection. Eight of the 11 macaques infected with SIVmac239 were killed due to AIDS symptoms after 2-4.5 years, while four of the five macaques

To investigate the dynamics of spread of simian immunodeficiency virus (SIV) in the lymphoid organs, we sequentially analyzed the viral burden in lymph nodes

TY - JOUR. T1 - Construction and characterization of replication-competent simian immunodeficiency virus vectors that express gamma interferon. AU - Giavedoni, Luis D.. AU - Yilma, Tilahun. PY - 1996. Y1 - 1996. N2 - We report the construction and characterization of several replication- competent simian immunodeficiency virus (SIV) vectors with a deletion in the viral nef gene (SIV(Δnef)) that express gamma interferon (IFN-γ). The expression of the cytokine gene was controlled either by the simian virus 40 early promoter or by the SIV 5 long terminal repeat regulatory sequences, utilizing the nef gene splice signals. To enhance the expression of IFN-γ, the two in-frame nef start codons were mutated without altering the Env amino acid sequence (SIV(Hy-IFN)). Plasmids containing full-length proviral genomes were used to obtain high-titer stocks of each recombinant virus in cell cultures. Expression of IFN-γ by SIV(HyIFN) reached levels as high as 106 U/ml after 11 days in culture. The IFN-γ ...

TY - JOUR. T1 - Structured treatment interruptions with tenofovir monotherapy for simian immunodeficiency virus-infected newborn macaques. AU - Van Rompay, Koen K.A.. AU - Singh, Raman P.. AU - Heneine, Walid. AU - Johnson, Jeffrey A.. AU - Montefiori, David C.. AU - Bischofberger, Norbert. AU - Marthas, Marta. PY - 2006/7/1. Y1 - 2006/7/1. N2 - We demonstrated previously that prolonged tenofovir treatment of infant macaques, starting early during infection with virulent simian immunodeficiency virus (SIVmac251), can lead to persistently low or undetectable viremia even after the emergence of mutants with reduced in vitro susceptibility to tenofovir as a result of a K65R mutation in reverse transcriptase; this control of viremia was demonstrated to be mediated by the generation of effective antiviral immune responses. To determine whether structured treatment interruptions (STI) can induce similar immunologic control of viremia, eight newborn macaques were infected with highly virulent SIVmac251 ...

Determination of KP metabolites in plasma were determined using three separate LC/MS/MS methods. A 5-analyte method was used for simultaneous analysis of KYN, KYNA, 3HK, AA, and 3HAA. A second method was used for analysis of QA, and a third method was employed to quantitate TRP in plasma. The stability of KP metabolites in plasma following storage at −20°C up to 3 mo and following the freeze-thaw cycle was established prior to analysis of the samples. For the 5-analyte method, a 200-μl aliquot of plasma was first mixed with 25 μl of 10% ascorbic acid followed by the addition of 50 μl of internal standard solution (acetonitrile/water; 50:50) containing KYN-D6 (100 ng/ml), KYNA-D5 (50 ng/ml), 15N13C2 3HK (100 ng/ml), and 13C6 AA (50 ng/ml). To this mixture, 800 μl of acetonitrile/methanol (90:10; v/v) was added to precipitate the proteins. After mixing and centrifugation, a 700-μl aliquot of supernatant was transferred to a clean tube and evaporated at 40°C for up to 2 h using TurboVap. ...

TY - JOUR. T1 - Vaccine protection of rhesus macaques against simian immunodeficiency virus infection. AU - Carlson, J. R.. AU - McGraw, T. P.. AU - Keddie, E.. AU - Yee, J. L.. AU - Rosenthal, A.. AU - Langlois, A. J.. AU - Dickover, R.. AU - Donovan, R.. AU - Luciw, P. A.. AU - Jennings, M. B.. AU - Gardner, M. B.. PY - 1990. Y1 - 1990. N2 - Rhesus macaques (Macaca mulatta) immunized with an inactivated whole SIV(mac) vaccine and muramyl dipeptide (MDP), incomplete Freunds adjuvant (IFA), or aqueous suspension were challenged intravenously with 0.1 TCID50 of cell-free SIV(mac). Whereas virus was readily recovered from the peripheral blood lymphocytes of 10 of 10 nonvaccinated controls following this challenge dose, virus was not recovered from the three animals that received the vaccine with MDP nor from one of two animals that received the vaccine with IFA and one of three animals that received the aqueous vaccine. The animals that were protected against challenge were those that had ...

Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation …

A reliable method for the quantitation of plasma viremia in nonhuman primates infected with simian immunodeficiency virus (SIV) and related viruses is described. This method is based on an established quantitative-competitive PCR format and includes a truncated control for internal assay calibration. Optimization of assay conditions has significantly improved amplification specificity, and interassay variability is comparable to that of commercially available assays for human immunodeficiency virus (HIV) quantitation. This procedure was used to monitor viral loads in a group of Macaca mulatta animals that were infected with SIVsmE660 for over 2 years. Highly diverse profiles of plasma viremia were observed among animals, and high viral loads were associated with more rapid disease progression. Spearman rank correlation analyses were done for survival versus three parameters of viral load: plasma viremia, p27 core antigen, and frequency of infected peripheral blood mononuclear cells. Plasma ...

TY - JOUR. T1 - Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines. AU - Fukazawa, Yoshinori. AU - Park, Haesun. AU - Cameron, Mark J.. AU - Lefebvre, Francois. AU - Lum, Richard. AU - Coombes, Noel. AU - Mahyari, Eisa. AU - Hagen, Shoko I.. AU - Bae, Jin Young. AU - Reyes, Marcelo Delos. AU - Swanson, Tonya. AU - Legasse, Alfred W.. AU - Sylwester, Andrew. AU - Hansen, Scott. AU - Smith, Andrew T.. AU - Stafova, Petra. AU - Shoemaker, Rebecca. AU - Li, Yuan. AU - Oswald, Kelli. AU - Axthelm, Michael. AU - McDermott, Adrian. AU - Ferrari, Guido. AU - Montefiori, David C.. AU - Edlefsen, Paul T.. AU - Piatak, Michael. AU - Lifson, Jeffrey D.. AU - Sékaly, Rafick P.. AU - Picker, Louis. PY - 2012/11. Y1 - 2012/11. N2 - Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree ...

Simian immunodeficiency virus (SIV) gag-specific major histocompatibility complex (MHC)-restricted cytotoxic T-lymphocyte (CTL) activity was elicited in four out of six cynomolgus macaques after two immunizations with SIV gag recombinant vaccinia virus (rVV). No activity could be seen in three out of three non-immunized control animals. Low levels of anti-gag antibody were also seen in the same four responding animals. Virus-specific, MHC-restricted CTL are thought to give some protection and to assist in recovery in viral infection, and the induction of such CTL following vaccination with a single viral protein should act as an encouragement to those proposing similar vaccination studies in man.

A highly conserved threonine near the C terminus of gp120 of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) was investigated for its contributions to envelope protein function and virion infectivity. When this highly conserved Thr residue was substituted with anything other than serine (the other amino acid that can accept O-glycosylation), the resulting virus was noninfectious. We found that this Thr was critical for the association of gp120 with the virion and that amino acid substitution increased the amount of dissociated gp120 in the cell culture supernatant. When HIV virions were generated in cells overexpressing polypeptide N-acetylgalactosaminyltransferase 1 (GalNAcT1), viral infectivity was increased 2.5-fold compared to that of virus produced in wild-type HEK293T cells; infectivity was increased 8-fold when the Thr499Ser mutant was used. These infectivity enhancements were not observed when GalNAcT3 was used. Using HEK293T knockout cell lines totally devoid ...

In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression. Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses. Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival. The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival. These results suggest that proliferating CD4+ T cells function both as ...

African green monkeys (AGM) and sooty mangabeys (SM) are well-studied natural hosts of simian immunodeficiency virus (SIV) that do not progress to AIDS when

TY - JOUR. T1 - Route of simian immunodeficiency virus inoculation determines the complexity but not the identity of viral variant populations that infect rhesus macaques. AU - Greenier, J. L.. AU - Miller, C. J.. AU - Lu, D.. AU - Dailey, P. J.. AU - Lü, F. X.. AU - Kunstman, K. J.. AU - Wolinsky, S. M.. AU - Marthas, M. L.. PY - 2001. Y1 - 2001. N2 - A better understanding of the host and viral factors associated with human immunodeficiency virus (HIV) transmission is essential to developing effective strategies to curb the global HIV epidemic. Here we used the rhesus macaque-simian immunodeficiency virus (SIV) animal model of HIV infection to study the range of viral genotypes that are transmitted by different routes of inoculation and by different types of viral inocula. Analysis of transmitted variants was undertaken in outbred rhesus macaques inoculated intravenously (IV) or intravaginally (IVAG) with a genetically heterogeneous SIVmac251 stock derived from a well-characterized rhesus ...

Although the cellular immune response is essential for controlling SIV replication in Asian macaques, its role in maintaining nonpathogenic SIV infection in natural hosts such as sooty mangabeys (SM) remains to be defined. We have previously shown that similar to rhesus macaques (RM), SM are able to mount a T lymphocyte response against SIV infection. To investigate early control of SIV replication in natural hosts, we performed a detailed characterization of SIV-specific cellular immunity and viral control in the first 6 mo following SIV infection in SM. Detection of the initial SIV-specific IFN-γ ELISPOT response in SIVsmE041-infected SM coincided temporally with a decline in peak plasma viremia and was similar in magnitude, specificity, and breadth to SIVsmE041-infected and SIVmac239-infected RM. Despite these similarities, SM showed a greater reduction in postpeak plasma viremia and a more rapid disappearance of productively SIV-infected cells from the lymph node compared with ...

Immunization of rhesus macaques with strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection elicits T-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted SIV, but not neutralization-resistant primary isolates of SIV. In an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle SIV (scSIV) that express envelope glycoproteins modified to lack structural features thought to interfere with the development of neutralizing antibodies. These envelope-modified strains of scSIV lacked either five potential N-linked glycosylation sites in gp120, three potential N-linked glycosylation sites in gp41, or 100 amino acids in the V1V2 region of gp120. Three doses consisting of a mixture of the three envelope-modified strains of scSIV were administered on weeks 0, 6, and 12, followed by two booster inoculations with vesicular stomatitis virus (VSV) G trans-complemented scSIV on

Opportunistic infections in human immunodeficiency virus (HIV)-infected persons have been shown to increase the rate of HIV replication. In populations where prophylaxis against Pneumocystis pneumonia is utilized, bacterial pneumonia is now the leading cause of lower respiratory tract infection in HIV+ patients. Our prior studies have shown that chronic alcohol consumption in demarcated simian immunodeficiency virus (SIV)-infected rhesus macaques increases plasma viral load set point and accelerates progression to end-stage acquired immune deficiency syndrome. While chronic alcohol abuse is well known to increase the incidence and severity of bacterial pneumonia, the impact of alcohol consumption on local and systemic SIV/HIV burden during lung infection is unknown. Therefore, we utilized the macaque SIV infection model to examine the effect of chronic ethanol (EtOH) feeding on SIV burden during the course of pulmonary infection with Streptococcus pneumoniae, the most commonly identified ...

We have investigated the molecular basis of biological differences observed among cell line-adapted isolates of the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and the simian immunodeficiency virus (SIV) in response to receptor binding by using a soluble form of CD4 (sCD4) as a receptor mimic. We find that sCD4 binds to the envelope glycoproteins of all of the HIV-1 isolates tested with affinities within a threefold range, whereas those of the HIV-2 and SIV isolates have relative affinities for sCD4 two- to eightfold lower than those of HIV-1. Treatment of infected cells with sCD4 induced the dissociation of gp120 from gp41 and increased the exposure of a cryptic gp41 epitope on all of the HIV-1 isolates. By contrast, neither dissociation of the outer envelope glycoprotein nor increased exposure of the transmembrane glycoprotein was observed when sCD4 bound to HIV-2- or SIV-infected cells. Moreover, immunoprecipitation with sCD4 resulted in the coprecipitation of the surface and

This chapter summarizes advances in the following areas: (1) dendritic cell (DC)-mediated simian immunodeficiency virus (SIV) transmission, (2) role of DCs in innate and adaptive immunity against...

Blum, F. C., Hardy, B. L., Bishop-Lilly, K, A., Frey, K. G., Hamilton, T., Whitney, J. B., Lewis, M. G., Merrell, D. S., and Mattapallil, J. 2020. Microbial dysbiosis during Simian immunodeficiency virus infection is partially reverted with combination anti-retroviral therapy. Scientific Reports: 10(1):6387.. George, J., Johnson, R. C., Mattapallil, M. J., Renn, L., Rabin, R., Merrell, D. S and Mattapallil, J. J. 2019. Gender differences in innate responses and gene expression profiles in memory CD4 T cells are apparent very early during acute simian immunodeficiency virus infection. PLoS One. 14(9):e0221159. Valiant, W. G., Mattapallil, M. J., Higgs, S., Huang, Y. S., Vanlandingham, D. L., Lewis, M. G and Mattapallil, J. 2019. Simultaneous coinfection of macaques with zika and dengue viruses does not enhance acute viremia but leads to activation of monocyte subsets and biphasic release of pro-inflammatory cytokines. Scientific Reports: 9: 7877 (1-11).. Valiant, W. G., Huang, Y., Vanlandingham, ...

The interplay between host and virus that controls disease progression in HIV- and SIV-infected individuals is undoubtedly complex. Host factor(s) play a major role in this process, however, because in the SIV-infected macaque, differences in disease progression and survival persist even though identical virus stocks, doses, and routes of inoculation are used for infection. We have developed a simplified in vitro assay that significantly correlated with disease progression after infection in vivo. The amount of virus produced from primary CD4+ T cells obtained from uninfected monkeys and infected in vitro correlated significantly with the rate of disease progression and survival after inoculation of the animal. The goal of this dissertation was to conduct a detailed molecular and immunological analysis of why differential in vivo virus production occurs and how it relates to disease progression and survival.Analyses of the events occurring during virus infection in vivo revealed two findings: 1) ...

TY - JOUR. T1 - A single amino acid change and truncated TM are sufficient for simian immunodeficiency virus to enter cells using CCR5 in a CD4-independent pathway. AU - Bonavia, A.. AU - Bullock, B. T.. AU - Gisselman, K. M.. AU - Margulies, B. J.. AU - Clements, Janice E. PY - 2005/10/10. Y1 - 2005/10/10. N2 - Entry of HIV and SIV into susceptible cells is mediated by CD4 and chemokine receptors, which act as coreceptors. To study cell entry of SIV, we constructed a cell line, xKLuSIV, derived from non-susceptible human K562 cells, that express the firefly luciferase reporter gene under control of a minimal SIV long terminal repeat (LTR). Using these susceptible cells, we studied the entry of a well-characterized molecularly cloned macrophage-tropic SIV. xKLuSIV cells that express rhesus macaque CD4 and/or the rhesus chemokine receptor CCR5 are susceptible to infection with the macrophage-tropic, neurovirulent strain SIV/17E-Fr, but only xKLuSIV cells expressing both CCR5 and CD4 were ...

猴免疫缺陷病毒（英语：Simian immunodeficiency virus，简称SIV），也称为非洲绿猴病毒（英语：African Green Monkey virus），是一种可影响至少33种非洲灵长目的逆转录病毒。[1][2]在对比奥科岛（于大约11000年前因海平面上升而从大陆隔离出来的一座岛屿）的四种猴中所发现的病毒株进行分析后，科学家们得出结论，称SIV在猴和猿中至少已存在了32000年，且实际存在时间可能比这长得多。[3][4] 这些灵长目动物中的两个物种中存在的病毒株，即白顶白眉猴（英语：sooty mangabey）体内的SIVsmm和黑猩猩体内的SIVcpz，被认为已跨越了种间屏障而进入人体，并最终成为了HIV的两个亚型，即HIV-2和HIV-1。HIV-1转移到人体最可能的路径之一是人类与黑猩猩（在非洲常作为丛林肉的来源而被捕猎）血液的接触。[3] ...

Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

Genetic and antigenic variation may be one means by which lentiviruses that cause AIDS avoid elimination by host immune responses. Genetic variation in the envelope gene (env) was studied by comparing the nucleotide sequences of 27 clones obtained from two rhesus monkeys infected with molecularly cloned simian immunodeficiency virus. All 27 clones differed from each other and differed from the input clone in the gp120 (SU) portion of the envelope gene. Nucleotide substitutions were shown to accumulate with time at an average rate of 8.5 per 1,000 per year in SU. Surprisingly, the majority of nucleotide substitutions (81%) resulted in amino acid changes. Variation in SU was not random but occurred predominantly in five discrete regions. Within these variable regions, a remarkable 98% of the nucleotide substitutions changed the amino acid. These results demonstrate that extensive sequence variability accumulates in vivo after infection with molecularly cloned virus and that selection occurs in vivo for

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TY - JOUR. T1 - Homeostatic cytokines induce CD4 downregulation in African green monkeys Independently of antigen exposure to generate simian immunodeficiency Virus-Resistant CD8αα T cells. AU - Perkins, Molly R.. AU - Briant, Judith A.. AU - Calantone, Nina. AU - Whitted, Sonya. AU - Vinton, Carol L.. AU - Klatt, Nichole R.. AU - Ourmanov, Ilnour. AU - Ortiz, Alexandra M.. AU - Hirsch, Vanessa M.. AU - Brenchley, Jason M.. PY - 2014. Y1 - 2014. N2 - African green monkeys (AGMs; genus Chlorocebus) are a natural host of simian immunodeficiency virus (SIVAGM). As they do not develop simian AIDS, there is great interest in understanding how this species has evolved to avoid immunodeficiency. Adult African green monkeys naturally have low numbers of CD4+ T cells and a large population of major histocompatibility complex class II-restricted CD8αdim T cells that are generated through CD4 downregulation in CD4+ T cells. Mechanisms that drive this process of CD4 downregulation are unknown. Here, we ...

Major histocompatibility complex (MHC) molecules expressed on the surface of human immunodeficiency virus (HIV) are potential targets for neutralizing antibodies. Since MHC molecules are polymorphic, nonself MHC can also be immunogenic. We have used combinations of novel recombinant HLA class I and II and HIV/simian immunodeficiency virus (SIV) antigens, all linked to dextran, to investigate whether they can elicit protective immunity against heterologous simian/human immunodeficiency virus (SHIV) challenge in rhesus macaques. Three groups of animals were immunized with HLA (group 1, n = 8), trimeric YU2 HIV type 1 (HIV-1) gp140 and SIV p27 (HIV/SIV antigens; group 2, n = 8), or HLA plus HIV/SIV antigens (group 3, n = 8), all with Hsp70 and TiterMax Gold adjuvant. Another group (group 4, n = 6) received the same vaccine as group 3 without TiterMax Gold. Two of eight macaques in group 3 were completely protected against intravenous challenge with 18 50% animal infective doses (AID(50)) of ...

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A post we made last week suggested a new vaccine can protect macaques against the monkey equivalent of HIV, however the vaccine using the common virus cytomegalovirus (CMV) as the vector or container of proteins from the simian immunodeficiency virus (SIV) protected none of a group of 24 rhesus macaques from infection. But in 13…

At the end of the recovery period after huOKT4 treatment, the CD4+ TN-depleted cohort manifested almost a complete absence of circulating CD4+ TN cells. Importantly, no CD4+ TN regeneration was observed throughout the entire course of SIV infection in the CD4+ TN-depleted cohort, in sharp contrast to the CD4+ TN-repleted RMs (Fig. 2 B). CD4+ TN lack CCR5 expression, and are thus not primary targets of CCR5-tropic SIV (Picker et al., 2004). Therefore, given the essentially equivalent CD4+ TM populations in the CD4+ TN-depleted and -repleted cohorts (Fig. 1), it is not surprising that the absence of CD4+ TN in the former group had no effect on peak pvl (Fig. 2 C). More surprising was the observation that early plateau- and chronic-phase pvl were also not significantly different between the CD4+ TN-depleted and -repleted groups (Fig. 2 C), despite the facts that SIV-specific CD4+ T cell responses were essentially absent in CD4+ TN-depleted RMs during acute infection (Fig. 2 D), and that only 11% of ...

The human T-lymphotropic viruses, type I (HTLV-I) and type II (HTLV-II), are closely related but distinct retroviruses that can infect humans. They are different from the human immunodeficiency viruses that cause acquired immunodeficiency syndrome. Screening of the U.S. blood supply for HTLV-I/II, which began in 1988, identifies HTLV-I- and HTLV-II-infected persons who should be counseled regarding their infections. This document summarizes CURRENT information about HTLV, types I and II, and presents recommendations developed by CDC and a U.S. Public Health Service working group for counseling HTLV-I- and HTLV-II-infected persons ...

The RAPAd® method of Adenovirus construction, developed by ViraQuest Inc. scientists, has been used by other scientists around the world.. Request Quote ...

What type of virus is HIV? HIV is a lentivirus, and like all viruses of this type, it attacks the immune system. Lentiviruses are in turn part of a larger group of viruses known as retroviruses. The name lentivirus literally means slow virus because they take such a long time to produce any adverse effects in the body. They have been found in a number of different animals, including cats, sheep, horses and cattle. However, the most interesting lentivirus in terms of the investigation into the origins of HIV is the Simian Immunodeficiency Virus (SIV) that affects monkeys, which is believed to be at least 32,000 years old.1 So did HIV come from an SIV? It is now thought that HIV came from a similar virus found in chimpanzees. It is now thought that HIV came from a similar virus found in chimpanzees. It is now generally accepted that HIV is a descendant of a Simian Immunodeficiency Virus because certain strains of SIVs bear a very close resemblance to HIV-1 and HIV-2, the two types of HIV. ...

Immunosuppressive CD4+CD25+FoxP3+ regulatory T (Treg) cells, which play a pivotal role in peripheral tolerance [1], have also been found to play a role in the immunopathogenesis of disease caused by certain persistent infections [2,3]. The overall impact of Treg cells on HIV/simian immunodeficiency virus (SIV) disease progression remains controversial and has proven difficult to assess due to lack of specific inhibitors of Treg-cell activity and the complex role of immune activation in HIV/SIV disease. Treg cells potentially exert contrasting effects: slowing progression by suppressing generalized immune hyperactivation and HIV replication in non-Treg cells, or accelerating progression by suppressing virus-specific immune responses, and/or contributing to the loss of T helper-17 cells, thereby increasing immune activation mediated by microbial translocation from the gut [3-7]. Although there is conflicting data regarding the frequency of Treg cells in the blood during the course of infection, it ...

TY - JOUR. T1 - Rare Control of SIVmac239 Infection in a Vaccinated Rhesus Macaque. AU - Martins, Mauricio A.. AU - Tully, Damien C.. AU - Shin, Young C.. AU - Gonzalez-Nieto, Lucas. AU - Weisgrau, Kim L.. AU - Bean, David J.. AU - Gadgil, Rujuta. AU - Gutman, Martin J.. AU - Domingues, Aline. AU - Maxwell, Helen S.. AU - Magnani, Diogo M.. AU - Ricciardi, Michael. AU - Pedreño-Lopez, Nuria. AU - Bailey, Varian. AU - Cruz, Michael A.. AU - Lima, Noemia S.. AU - Bonaldo, Myrna C.. AU - Altman, John D.. AU - Rakasz, Eva. AU - Capuano, Saverio. AU - Reimann, Keith A.. AU - Piatak, Michael. AU - Lifson, Jeffrey D.. AU - Desrosiers, Ronald C.. AU - Allen, Todd M.. AU - Watkins, David I.. PY - 2017/8. Y1 - 2017/8. N2 - Effector memory T cell (TEM) responses display potent antiviral propertis and have been linked to stringent control of simian immunodeficiency virus (SIV) replication. Since recurrent antigen stimulation drives the differentiation of CD8+ T cells toward the TEM phenotype, in this study ...

Increasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic strategies. We therefore explored the role of antigen-specific immune responses in controlling plasma viremia in SIV infected rhesus macaques. Thirteen rhesus macaques were inoculated either intravaginally or intrarectally with SIVMAC251. Peripheral blood CD4+ T-cells were quantified. Plasma was examined for viremia, antigen specific IgG, IgA and IgM binding responses and neutralizing antibodies. Regions containing binding epitopes for antigen-specific IgG, IgM and IgA responses were determined, and the minimum size of linear Envelope epitope responsible for binding antibodies was identified. The presence of neutralizing antibodies did not correlate the outcome of the disease. In a few SIV-infected macaques, antigen-specific IgG and IgM responses in plasma

The sexual transmission of viruses is responsible for the spread of multiple infectious diseases. Although the human immunodeficiency virus (HIV)/AIDS pandemic remains fueled by sexual contacts with infected semen, the origin of virus in semen is still unknown. In a substantial number of HIV-infected men, viral strains present in semen differ from the ones in blood, suggesting that HIV is locally produced within the genital tract. Such local production may be responsible for the persistence of HIV in semen despite effective antiretroviral therapy. In this study, we used single-genome amplification, amplicon sequencing ( gene), and phylogenetic analyses to compare the genetic structures of simian immunodeficiency virus (SIV) populations across all the male genital organs and blood in intravenously inoculated cynomolgus macaques in the chronic stage of infection. Examination of the virus populations present in the male genital tissues of the macaques revealed compartmentalized SIV populations in testis,

Macaque immunization with a mixture of four SIV peptides from conserved hydrophilic envelope regions has been shown to prevent virus persistence following challenge with SIVmne/E11s. Data shown here demonstrate that lymph node cells from all vaccinated monkeys and peripheral blood lymphocytes from one of the vaccinees were positive in a SIV-pol nested polymerase chain reaction (PCR) amplification analysis. However, by 37 months after infection, all immunized monkeys were healthy while two of three controls had died and the remaining animal was virus culture-positive and had declining CD4+ lymphocytes. Viable lymph node cells and peripheral lymphoid cells in blood were transferred from the three immunized macaques to individual susceptible macaques. As a control for the transfer, one of the vaccine experiment controls that was actively producing virus in its peripheral blood was used. None of the recipients of cells from the vaccinated macaques seroconverted and all were virus coculture- and ...

A similar situation was noted in lingual tonsil, which consists of many lymphoid nodules, each connected to the pharynx by an invaginating crypt. The number of infected cells varied from one tonsil nodule to another, but most nodules were infected, and infected cells were numerous especially in p55-negative regions of the ELT (Fig. 4D). In the lingual tonsil at day 7, 74% of infected cells were in ELT, 6% in LE, and 20% in GCs.. We expected that productive infection with SIV would begin in stratified squamous epithelium that constitutes the external covering of the tonsil (Fig. 4B), tongue (Fig. 4D), and buccal cavity (21). This epithelium is comparable to the surface of the vagina and anus, and is rich in DCs that can capture and transport immunodeficiency viruses (13-17). When we infected the monkeys, we applied SIV directly to the tonsillar squamous epithelium. Breaks in this epithelium also could have provided a conduit for SIV to access susceptible lymphocytes. However, infected cells were ...

The potential impact of this CD4+ memory proliferative collapse on peripheral tissues was revealed by another series of observations. First, as explained in Results, both the kinetics of BrdU labeling of blood, lymph node, and BAL T cells, and the pattern of Ki-67 expression by these labeled cells, firmly establish that the pulmonary tissue-air interface of SIV-infected normal progressors is constantly being seeded by recently divided CD4+ memory T cells, originating elsewhere (likely organized lymphoid tissues). Thus, SIV infection increases CD4+ memory T cell proliferation in peripheral lymphoid tissues, producing progeny that directly disperse to extralymphoid effector sites. Because there is both a paucity of Ki-67high T cells and minimal immediate BrdU uptake by T cells in BALs, these cells do not appear to further proliferate in these sites, but given the rapid decline in BrdU labeling observed in our BAL samples (Fig. 7), likely die in situ, only to be continuously replaced by subsequent ...

TY - JOUR. T1 - A panel of IgG1 b12 variants with selectively diminished or enhanced affinity for Fcγ receptors to define the role of effector functions in protection against HIV. AU - Moldt, Brian. AU - Schultz, Niccole. AU - Dunlop, D. Cameron. AU - Alpert, Michael D.. AU - Harvey, Jackson D.. AU - Evans, David T.. AU - Poignard, Pascal. AU - Hessell, Ann J.. AU - Burton, Dennis R.. PY - 2011/10/1. Y1 - 2011/10/1. N2 - Passive transfer of neutralizing antibodies is effective in protecting rhesus macaques against simian/human immunodeficiency virus (SHIV) challenge. In addition to neutralization, effector functions of the crystallizable fragment (Fc) of antibodies are involved in antibody-mediated protection against a number of viruses. We recently showed that interaction between the Fc fragment of the broadly neutralizing antibody IgG1 b12 and cellular Fcγ receptors (FcγRs) plays an important role in protection against SHIV infection in rhesus macaques. The specific nature of this ...

Examining the differences and similarities between HIV and SIV retroviral replication systems is important in light of the fact that SIV animal models are used in the development and testing of HIV eradicating drugs and vaccines. One such difference may be the efficiency of Gag directed viral assembly. Studies with HIV-1 Gag have shown that during the late phase retroviral replication, 1,500-5,000 copies of Gag are targeted to lipid raft sites on the plasma membrane for new virus production.,super,2; 3; 4,super, The role of MA as a domain of Gag/Gag-Pro-Pol is crucial for viral particle assembly and budding through the synergistic properties of the myristate group and positively charged basic residues of the N-terminus. Work done by Tang ,italic,et al,italic,.,super,5,super, demonstrated myristylated [myr(+)] HIV-1 MA exists in an equilibrium between a monomeric and trimeric state. Concentration dependent assays done with 2D ,super,1,super,H, ,super,15,super,N-HSQC NMR showed the chemical shift ...

p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...

An important step in combating infectious diseases like HIV is exploring the origin and evolution of the disease. Simian immunodeficiency virus (SIV) is the equivalent of HIV for monkeys and chimpanzees. It is believed that HIV arose from SIV, which was then transmitted to humans by contact with chimpanzees. In a study published in PLoS Pathogens, scientists from the University of Arizona in Tucson have found that SIV may have infected the African green monkey population much later than previously thought.

Using enhanced green fluorescence protein (EGFP-1), a transient transfection reporter system was established to monitor the transcriptional activity of the long terminal repeats (LTR) of several primary strains of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus SIVmac239. After transient transfection of HeLa cells with variant HIV-1 LTR-EGFP-1 constructs, we scanned the cell culture using fluorescent activated cell sorter (FACS). Using FACS it was possible to simultaneously estimate for transfection efficiency and to quantitatively determine the fluorescence intensity of the transfected population. Data showed that expression of EGFP-1 was DNA dose dependent. FACS enabled the visualization of heterogeneity in the level of reporter gene expression in a transiently transfected population. The distribution of the fluorescent intensity of transfected cells was treated as a frequency distribution, and different statistical estimators were used to quantitate the amount of ...

TY - JOUR. T1 - Relationship of neurologic status in macaques infected with the simian immunodeficiency virus to cerebrospinal fluid quinolinic acid and kynurenic acid. AU - Heyes, Melvyn P.. AU - Jordan, Elaine K.. AU - Lee, Kristin. AU - Saito, Kuniaki. AU - Frank, Joseph A.. AU - Snoy, Phillip J.. AU - Markey, Sanford P.. AU - Gravell, Maneth. PY - 1992/1/20. Y1 - 1992/1/20. N2 - Increased concentrations of the excitotoxin quinolinic acid (QUIN) have been implicated in the neurologic deficits and brain atrophy that may accompany infection with the human immunodeficiency virus type-1. Key neuropathologic features of the AIDS encephalitis are replicated in some macaques following infection with the simian immunodeficiency virus (SIV). In the present studies, cerebrospinal fluid (CSF) QUIN concentrations increased within 2 weeks following infection of 11 rhesus macaques (Macaca mulatta) with a neurotropic sooty mangabey isolate of the simian immunodeficiency virus (SIVsm) and were sustained to , ...

Looking for online definition of simian-human immunodeficiency virus in the Medical Dictionary? simian-human immunodeficiency virus explanation free. What is simian-human immunodeficiency virus? Meaning of simian-human immunodeficiency virus medical term. What does simian-human immunodeficiency virus mean?

Infection of macaques with attenuated simian immunodeficiency virus (SIV) induces potent superinfection resistance that may be applicable to the development of an AIDS vaccine but little information exists concerning the conditions necessary for the induction of this vaccine effect. We report that only a high dose of attenuated SIVmac protected macaques against intravenous challenge with more virulent virus 15 weeks after primary infection. Three of four animals given 2000-20000 TCID50 of SIVmacC8, a molecular clone of SIVmac251(32H) with a 12 bp deletion in the nef gene, essentially resisted superinfection with uncloned SIVmac. In two animals challenge virus was never detected by PCR and in one animal challenge virus was detected on one occasion only. Although animals given 2-200 TCID50 of attenuated virus were superinfected they were spared from the loss of CD4 cells seen in infected naive controls. Protection from superinfection did not correlate with immune responses, including the levels of virus

To gain a better understanding of the assembly process in simian immunodeficiency virus (SIV), we first established the conditions under which recombinant SIV Gag lacking the C-terminal p6 domain (SIV GagΔp6) assembled in vitro into spherical particles. Based on the full multimerization capacity of SIV GagΔp6, and to identify the Gag sequences involved in homotypic interactions, we next developed a pull-down assay in which a panel of histidine-tagged SIV Gag truncation mutants was tested for its ability to associate in vitro with GST-SIVGagΔp6. Removal of the nucleocapsid (NC) domain from Gag impaired its ability to interact with GST-SIVGagΔp6. However, this Gag mutant consisting of the matrix (MA) and capsid (CA) domains still retained 50% of the wild-type binding activity. Truncation of SIV Gag from its N-terminus yielded markedly different results. The Gag region consisting of the CA and NC was significantly more efficient than wild-type Gag at interacting in vitrowith GST-SIVGagΔp6. ...

Like most emerging infectious disease viruses, HIV is also of zoonotic origin. To assess the risk for cross-species transmission of simian immunodeficiency viruses (SIVs) from nonhuman primates to humans in the Democratic Republic of Congo, we collected 330 samples derived from nonhuman primate bushmeat at 3 remote forest sites. SIV prevalences were estimated by using a novel high-throughput assay that included 34 HIV and SIV antigens in a single well. Overall, 19% of nonhuman primate bushmeat was infected with SIVs, and new SIV lineages were identified. Highest SIV prevalences were seen in red-tailed guenons (25%) and Tshuapa red colobus monkeys (24%), representing the most common hunted primate species, thus increasing the likelihood for cross-species transmission. Additional studies are needed to determine whether other SIVs crossed the species barrier. With the newly developed assay, large-scale screening against many antigens is now easier and faster ...

Like most emerging infectious disease viruses, HIV is also of zoonotic origin. To assess the risk for cross-species transmission of simian immunodeficiency viruses (SIVs) from nonhuman primates to humans in the Democratic Republic of Congo, we collected 330 samples derived from nonhuman primate bushmeat at 3 remote forest sites. SIV prevalences were estimated by using a novel high-throughput assay that included 34 HIV and SIV antigens in a single well. Overall, 19% of nonhuman primate bushmeat was infected with SIVs, and new SIV lineages were identified. Highest SIV prevalences were seen in red-tailed guenons (25%) and Tshuapa red colobus monkeys (24%), representing the most common hunted primate species, thus increasing the likelihood for cross-species transmission. Additional studies are needed to determine whether other SIVs crossed the species barrier. With the newly developed assay, large-scale screening against many antigens is now easier and faster.

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American Association of Zoo Veterinarians Infectious Disease Committee Manual 2013 SIMIAN IMMUNODEFICIENCY VIRUSES Animal Group(s) Affected Found in many African nonhuman primates. Macaques susceptible. Transmission Clinical Signs Severity Treatment Prevention and Control Zoonotic Mainly horizontal through sexual contact and bite wounds. Clinical disease occurs in only a minority of infected individuals. Severe and fatal in nonnatural host Test collection and determine risk to benefit of introductions to naïve animals. Vertical transmission reported by virus-infected milk When pathogenic, disease depends on the nature of the organ and opportunistic infections. None specific although same treatment options for HIV could be used Infection should be considered a zoonotic disease since many SIV species can grow in human cell lines in vitro. Fact Sheet compiled by: Sam Rivera; updated by Natalie Mylniczenko Sheet completed on: 1 June 2011; updated 10 September 2013 Fact Sheet Reviewed by: William ...

Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity).

The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights the importance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and genetic mechanisms of protection against mucosal infection by the simian immunodeficiency virus (SIV). A plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251 or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect against SIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals, there was about a one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex class I allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among ...

Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged |5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV

Mitochondrial 12S and cytochrome B sequences were identical in all four animals and confirmed that the monkeys were M. sphinx [9, 10]. In addition, the cytochrome B sequences were indistinguishable from the recently described northern mandrill haplotype (Figure 1B) [10], suggesting that the captive animals descended from founders originating from a locale north of the Ogooué River (see Figure 1A). SIV-pol fragments could be amplified from PBMC of both adult mandrills CAS and REB with the primer set specific for SIVmnd2, but not with SIVmnd1 specific primers. However, analysis of the cloned fragments showed that these were 96-97% identical to SIVdrl-1FAO (GenBank acc. no. AY159321) isolated from a drill monkey (Mandrillus leucophaeus), with a lower sequence identity to SIVmnd2 (± 85% to GenBank acc. no. AF367411), and to SIVmnd1 (,64% to GenBank acc. no. M27470). Although SIVmnd2 and SIVdrl are more closely related to each other than the two SIVmnd strains, SIVdrl has several mismatches with ...

An env- and nef-deleted SHIV DNA, SIVGP1, was constructed from an infectious SHIVMD14YE clone DNA as described previously (13, 22). The DNA is deleted with a gene fragment encoding Env surface protein (SU; nucleotide [nt] 6211 to nt 7726 in HIV-1DH12; these sequence data are available from GenBank/EMBL/DDBJ under accession no. AF069140), the 3′ portion of the env gene (nt 8628 to nt 8764 in HIV-1DH12), and the 5′ quarter of the nef gene (nt 9333 to nt 9481 in SIVmac239; GenBank/EMBL/DDBJ accession no. M33262). From SIVGP1 DNA, the 5′ long terminal repeat region was replaced with a CMV promoter with immediate early enhancer and the 3′ portion containing the remaining nef and the 3′ long terminal repeat was replaced with Simian virus 40 poly A to obtain CMV-SHIVdEN DNA. Therefore, the CMV-SHIVdEN DNA has SIV-derived gag, pol, vif, vpx, and partial vpr sequences and HIV-1-derived partial vpr, tat, rev, and partial env (nt 7726 to nt 8628 containing the second exon of tat, the second exon ...

1. ShortmanK. LiuYJ. 2002. Mouse and human dendritic cell subtypes.. Nat Rev Immunol. 2. 151. 161. 2. AlmeidaM. CorderoM. AlmeidaJ. OrfaoA. 2005. Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection.. AIDS. 19. 261. 271. 3. BarronMA. BlyveisN. PalmerBE. MaWhinneyS. WilsonCC. 2003. Influence of plasma viremia on defects in number and immunophenotype of blood dendritic cell subsets in human immunodeficiency virus 1-infected individuals.. J Infect Dis. 187. 26. 37. 4. DonaghyH. PozniakA. GazzardB. QaziN. GilmourJ. 2001. Loss of blood CD11c(+) myeloid and CD11c(−) plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load.. Blood. 98. 2574. 2576. 5. GrassiF. HosmalinA. McIlroyD. CalvezV. DebreP. 1999. Depletion in blood CD11c-positive dendritic cells from HIV-infected patients.. AIDS. 13. 759. 766. 6. PacanowskiJ. KahiS. BailletM. LebonP. DeveauC. 2001. Reduced blood CD123+ (lymphoid) ...

Aikeqing (AKQ) has been shown in clinical studies to improve quality of life of HIV/AIDS patients, but anti-HIV activity has not been determined. The SHIV-infected macaque is an important animal model for testing antiviral drugs. This study aimed to determine the anti-HIV activity of AKQ in chronically SHIV89.6-infected Chinese rhesus macaques. Nine Chinese rhesus macaques were inoculated intravenously with SHIV89.6 virus. At 11 weeks post-infection, the animals were arbitrarily divided into three groups: high-dose (AKQ 1.65 g/kg; n = 3), low-dose (AKQ 0.55 g/kg; n = 3), and control (water 1 mL/kg; n = 3). Treatment was administered by the intragastric gavage route once-daily for 8 weeks. Blood (5 mL) was collected biweekly. Viral loads were analyzed by real-time quantitative RT-PCR assays, and T cell counts were monitored by FACS analyses throughout the treatment. AKQ induced a persistent decline (P = 0.02) in plasma viral loads during treatment in the high-dose group

Sigma-Aldrich offers abstracts and full-text articles by [Amrita Datta Chaudhuri, Sowmya V Yelamanchili, Maria Cecilia G Marcondes, Howard S Fox].

CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral load and disease progression following infection with HIV-1. An association has also been reported between CCL3L CNV and clinical sequelae of the simian immunodeficiency virus (SIV) infection in vivo in rhesus monkeys. The present study was initiated to explore the possibility of an association of CCL3L CNV with the control of virus replication and AIDS progression in a carefully defined cohort of SIVmac251-infected, Indian-origin rhesus monkeys. Although we demonstrated extensive variation in copy number of CCL3L in this cohort of monkeys, CCL3L CNV was not significantly associated with either peak or set-point plasma SIV RNA levels in these monkeys when MHC class I allele Mamu-A*01 was included in the models or progression to AIDS in these ...

Rhesus monkeys (Macaca mulatta) were experimentally infected with strains of simian immunodeficiency virus (SIV) derived from SIVmac239 lacking vpr, vpx, or both vpr and vpx genes. These auxiliary genes are not required for virus replication in cultured cells but are consistently conserved within the SIVmac/human immunodeficiency virus type 2/SIVsm group of primate lentiviruses. All four rhesus monkeys infected with the vpr deletion mutant showed an early spike in plasma antigenemia, maintained high virus burdens, exhibited declines in CD4+ lymphocyte concentrations, and had significant changes in lymph node morphology, and two have died to date with AIDS. The behavior of the vpr deletion mutant was indistinguishable from that of the parental, wild-type virus. Rhesus monkeys infected with the vpx deletion mutant showed lower levels of plasma antigenemia, lower virus burdens, and delayed declines in CD4+ lymphocyte concentrations but nonetheless progressed with AIDS to a terminal stage. The ...

In this study we immunophenotypically differentiate subpopulations of brain macrophages into perivascular macrophages and parenchymal microglia and demonstrate that perivascular macrophages are the major cell productively infected by SIV in the CNS of macaques. Preferential infection of perivascular macrophages in the CNS may account for several important observations concerning infection of the CNS, viral dynamics in the CNS, and the role of the CNS as a viral sanctuary or reservoir.. Although it has not been directly demonstrated, it is generally assumed that lentiviruses enter the CNS by the traffic of infected monocyte/macrophages (64). Our data showing that perivascular macrophages are the major cell type, infected in the brain, support this hypothesis. Studies in chimeric rodents and humans receiving bone marrow indicate that perivascular macrophages are continuously replaced from the circulation (15)(16)(17)(43). The immunophenotype described for perivascular macrophages, ...

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PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia(1). Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3-4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant ...

In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted |99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8+ T lymphocytes were |99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was |99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three

Human leukocyte antigen-E (HLA-E) normally presents an HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (SIV) vaccine generated Mamu-E (HLA-E homolog)-restricted T cell responses that mediated post-challenge SIV replication arrest in |50% of animals. However, HIV-1-specific, HLA-E-restricted T cells have not been observed in HIV-1-infected individuals. Here, HLA-E-restricted, HIV-1-specific CD8 + T cells were primed in vitro. These T cell clones and allogeneic CD8 + T cells transduced with their T cell receptors suppressed HIV-1 replication in CD4 + T cells in vitro. Vaccine induction of efficacious HLA-E-restricted HIV-1-specific T cells should therefore be possible.

In the past 30 years, HIV vaccine studies on traditional CD8+ T cell-targeted HIV vaccines were frustrated by the ineffectiveness of mediating immediate vaccinal interception upon infection acquisition prior to the explosive viral amplification. As the most important lesson of past HIV vaccine researches, the first hours to days immediately after viral infection might be the only vulnerable time period for immunologic interceptions.[1, 2] With this regard, immunologists started a novel research on employing Cytomegelovirus (CMV) as vaccine vector in early 2000s, to exploit CMV vectors unique ability on eliciting and maintaining abundant functional T cell responses at all potential HIV infection sites.[3-6] Recent CMV-based vaccine research, demonstrated by Louis Picker and colleagues, with statistical support by Dr. Edlefsen, manifests a remarkable infection control and clearance on ~50% of HIV-acquired rhesus macaques (RM) vaccinated by Simian immunodeficiency virus (SIV) inserted rhesus ...

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The membrane-proximal external region (MPER) of HIV-1, located at the C terminus of the gp41 ectodomain, is conserved and crucial for viral fusion. Three broadly neutralizing monoclonal antibodies (bnMAbs), 2F5, 4E10, and Z13e1, are directed against linear epitopes mapped to the MPER, making this conserved region an important potential vaccine target. However, no MPER antibodies have been definitively shown to provide protection against HIV challenge. Here, we show that both MAbs 2F5 and 4E10 can provide complete protection against mucosal simian-human immunodeficiency virus (SHIV) challenge in macaques. MAb 2F5 or 4E10 was administered intravenously at 50 mg/kg to groups of six male Indian rhesus macaques 1 day prior to and again 1 day following intrarectal challenge with SHIVBa-L. In both groups, five out of six animals showed complete protection and sterilizing immunity, while for one animal in each group a low level of viral replication following challenge could not be ruled out. The study ...

HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in ...

In this paper, the optimization of the conditionally live SIV-rtTA variant through viral evolution is described. We recently constructed this dox-dependent SIVmac239 variant by replacing the natural Tat-TAR mechanism of transcription control by the dox-inducible Tet-On regulatory mechanism. Although the original SIV-rtTA variant replicates in T cell lines and in primary macaque PBMC, it replicates poorly when compared with the parental SIVmac239 [25](Figs. 5 and 6). Upon long-term culturing, the virus acquired several mutations in the TAR and U3 region. These mutations significantly improve viral replication, but do not affect dox control. We thus generated novel SIV-rtTA variants that replicate efficiently and in a dox-dependent manner in both T-cell lines and primary macaque PBMC.. We previously used virus evolution to optimize a similarly constructed dox-dependent HIV-1 variant. Upon long-term culturing, this HIV-rtTA variant acquired several mutations in the rtTA and tetO components of the ...

A protease/anti-protease imbalance is a characteristic feature of inflammatory lung diseases such as cystic fibrosis (CF) and COPD. However, alpha-1-antitrypsin (AAT) enzyme replace- ment therapy (ERT) trials have not shown conclusive evidence of therapeutic benefit. Here, we assessed whether transduction of murine lungs with a pseudotyped SIV vector, rSIV.F/HN-hCEF-AAT, generates therapeutic levels of AAT. Mice were transduced with rSIV.F/HN-hCEF-AAT (1.4e8 TU/mouse) by nasal instillation and culled 10 days post-trans- duction. AAT levels in lung homogenate and epithelial lining fluid (ELF) were 3 logs above controls (p | 0.05), and hAAT concentration in ELF was 92-28lg/ml, similar to the thera- peutic AAT level in ELF of 70lg/ml. For comparison trans- fection of mouse lung with cationic lipid GL67A complexed to hCEFI-AAT only led to 0.4-0.1lg/ml AAT in ELF. A neutrophil elastase (NE) activity assay showed that the recombinant AAT successfully neutralised NE activity (p | 0.05). In a separate

Four glycoproteins of apparent molecular weights 300,000, 140,000, 125,000, and 36,000 (gp300, gp140, gp125, and gp36) are detectable in human immunodeficiency virus type 2 (HIV-2) infected cells. The gp125 and gp36 are the external and transmembrane components, respectively, of the envelope glycoproteins of HIV-2 mature virions. The gp300, which is a dimeric form of gp140, the precursor of HIV-2 envelope glycoprotein, is probably formed by a pH dependent fusion in the endoplasmic reticulum. Such a doublet is also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. On the other hand, the envelope glycoprotein precursor of HIV-1 does not form a dimer during its processing. Experiments carried out with various inhibitors of oligosaccharide trimming enzymes suggest that transient dimerization of the glycoprotein precursor is required for its efficient transport to the Golgi apparatus and for its processing. The gp300 is useful for detecting antibodies to

Lymphotropic papovavirus (LPV) and simian virus 40 (SV40) are members of the genus Polyomavirus (6). LPV was isolated from a B-lymphoblastic cell line derived from a lymph node of an apparently healthy African green monkey (18). In cell culture, LPV displays a highly restricted host range for continuous lines of B lymphoblasts of monkey or human origin (2, 3). Serological surveys of sera from humans and 11 different species of nonhuman primates, including rhesus monkeys, indicated that, with the exception of baboons, all showed evidence of infection by LPV or an antigenically related virus (14, 19).. Little is known of the natural biology of LPV. Because previous serological data suggested that LPV caused natural infections in different types of primates, we tested whether LPV might be detectable in simian immunodeficiency virus (SIV)-infected rhesus monkeys. We examined DNA that had been extracted for a previous study from brain tissue, peripheral blood mononuclear cells (PBMCs), or lymphoid ...

Researchers from the University of Nebraska Medical Center isolated and characterized EVs from the brains of rhesus macaques, both with and without simian immunodeficiency virus (SIV) induced central nervous system (CNS) disease. Small RNA sequencing revealed increased miR-21 levels in EVs from SIV encephalitic (SIVE)

A considerable body of evidence suggests that Fc-dependent functions improve the capacity of broadly neutralizing antibodies (BnAbs) to protect against and control HIV-1 infection. This phenomenon, however, has not been formally tested in robust cell-associated macaque simian-human immunodeficiency virus (SHIV) models with newer-generation BnAbs. We studied both the WT BnAb PGT121 and a LALA mutant of PGT121 (which has impaired Fc-dependent functions) for their ability to protect pigtail macaques from an i.v. high-dose cell-associated SHIVSF162P3 challenge. We found that both WT and LALA PGT121 completely protected all 12 macaques studied. Further, partial depletion of NK cells, key mediators of Fc-dependent functions, did not abrogate the protective efficacy of PGT121 in 6 macaques. Additionally, in animals with established SHIVSF162P3 infection, SHIV viremia levels were equally rapidly reduced by LALA and WT PGT121. Our studies suggest that the potent neutralizing capacity of PGT121 renders ...

Understanding the reasons why SIV-infected sooty mangabeys (SMs) remain healthy despite high viremia is a key unanswered question in contemporary AIDS research,...

An experimental drug called PMPA given to 25 macaque monkeys up to a day after they were exposed to simian immunodeficiency virus (SIV), an HIV-like ...

In the wild, infections by primate lentiviruses occur only among African monkeys and chimpanzees. Simian immunodeficiency viruses have been isolated from several species of monkeys. Based on sequence homology, the primate lentiviruses can be divided into several groups, of which only three are important from the perspective of primate models of AIDS: HIV-1/SIVcpz, HIV-2/SIVsmm/SIVmac, and SIVagm. The other primate lentiviruses, e.g., SIVmnd, SIVsyk, SIVwcm, SIVrcm, SIVdrl, etc., have not been used as yet to develop models of AIDS. The primate lentiviruses have little or no pathogenicity in their natural hosts and disease appears to result only after transmission to another species. ...

Attempts have been made earlier to determine structures of HIV-1 and simian immunodeficiency virus (SIV) PRs complexed with substrate oligopeptides (10, 12). In these attempts, the crystals of the complex were prepared by using the method of cocrystallization, in the hope that crystal formation preceded product release. However, in the crystals obtained, HIV-1 PR was found to be complexed with only the N-terminal (P) product peptide, whereas SIV PR was found to be complexed with a C-terminal (Q) product peptide. No structures with both products bound simultaneously were obtained (12). Through careful superpositions of the two product complexes, these authors have concluded that unacceptably close separations between scissile carbon and nitrogen atoms (1.3-2.2 Å) preclude the presence of both products in the active site during cocrystallization. In contrast, we have attempted to prepare the complex by the soaking method. Because, as has been shown here, soaking does not result in cleavage of the ...

Katti (Horng) Crakes, doctoral student in the schools of Medicine and Veterinary Medicine at UC Davis, served as first author on a UC Davis research study that found that the damaged gut lining (known as leaky gut) in monkeys infected with chronic simian immunodeficiency virus (SIV), an HIV-like virus, was rapidly repaired within five hours of receiving Lactobacillus plantarum bacteria. The outcome lends hope that leaky gut, a common condition among HIV patients, could be effectively treated in the future ...

A series of cationic metalloporphyrin-ellipticine complexes were found to inhibit the cytopathicity of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus in MT-4 cells at concentrations ranging from 1.4 to 17 micrograms/mL, i.e. at a concentration that was 2.5-30-fold below the cytotoxicity threshold. These compounds were also found to inhibit syncytium formation between persistently HIV-1-infected HUT-78 and uninfected Molt/4 cells, to interfere with HIV-1 binding to the cells, and to suppress HIV-1-associated reverse transcriptase activity ...

USE OF INTEGRASE INHIBITOR TO ASSESS THE CYTOTOXIC T LYMPHOCYTE RESPONSE DURING SIMIAN IMMUNODEFICIENCY VIRUS INFECTION IN RHESUS MACAQUES Abstract: The host immune response against human immunodeficiency virus (HIV) infection is multi-faceted, with the c...