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
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 ...
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 ...
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
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...
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.
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 ...
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,
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 ...
Interest in the lentivirus subfamily of retroviruses has greatly intensified due to the realization that HIV-1 and HIV-2 are members of this previously obscure group. Related lentiviruses have now bee
Matrix protein p17 targets Gag and Gag-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex. Implicated in the release from host cell mediated by Vpu (By similarity).
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
TY - JOUR. T1 - Spontaneous and antigen-induced production of HIV-inhibitory β- chemokines are associated with AIDS-free status. AU - Garzino-Demo, A.. AU - Moss, R. B.. AU - Margolick, Joseph Bernard. AU - Cleghorn, F.. AU - Sill, A.. AU - Blattner, W. A.. AU - Cocchi, F.. AU - Carlo, D. J.. AU - DeVico, A. L.. AU - Gallo, R. C.. PY - 1999. Y1 - 1999. N2 - The β-chemokines RANTES, macrophage inflammatory protein (MIP)-1α, and MIP-1β suppress infection by macrophage-tropic strains of HIV and simian immunodeficiency virus (SIV) by binding and down-regulating the viral coreceptor, CCR5. Accordingly, we have examined whether higher levels of CCR5 ligands are associated with a more favorable clinical status in AIDS. A cross-sectional study of 100 subjects enrolled in the Multicenter AIDS Cohort Study at the Baltimore site was conducted to measure chemokine production and lymphocyte proliferation by peripheral blood mononuclear cells (PBMC). Statistical analyses of the data revealed that the ...
Simian immunodeficiency viruses are retroviruses found in primates. Researchers have hypothesized that SIVs led to the transmission of HIV (human immunodeficiency virus) in humans. Evidence suggests that both HIV-1 and HIV-2 originated in Africa, with HIV-1 being a relative of a SIV that infects wild chimpanzees, and HIV-2 being a relative of one that infects the sooty mangabey. It is likely that the first human cases of HIV resulted from contact with an infected chimpanzee or monkey.. ...
As a cytokine with functions directed to inflammatory and immune cells as well as fibroblasts, interleukin-11 was selected to modulate invasive behaviour of fibroblasts. For transduction, a retroviral vector system, particle-mediated transfer (gene gun), and a lentiviral vector based on simian immunodeficiency virus were investigated. Cells (500,000) were injected directly into the knee joinst of mice with severe combined immunodeficiency (SCID). Mice were monitored for joint swelling, serological parameters and by radiological methods. In vitro, cells were coincubated with cartilage for 1 week. Finally, the histology of cartilage destruction and signs of apoptosis were studied. ...
Del Prete GQ, Scarlotta M, Newman L, Reid C, Parodi LM, Roser JD, Oswald K, Marx PA, Miller CJ, Desrosiers RC, Barouch DH, Pal R, Piatak M, Chertova E, Giavedoni LD, OConnor DH, Lifson JD, Keele BF. Comparative characterization of transfection- and infection-derived simian immunodeficiency virus challenge stocks for in vivo nonhuman primate studies. J Virol. 2013 Apr; 87(8):4584-95 ...
The identification of plasma viral RNA (35) and CD4+ T cell counts (37) as surrogate markers of HIV disease progression was instrumental in the development of ART for attaining improved clinical care in HIV-infected patients. As the HIV field rapidly turns toward achieving functional cure, there has been renewed interest in identifying biomarkers of viral rebound. Monitoring biomarkers will guide clinical trials with effective therapeutic candidates, minimizing the investment in those that are unlikely to result in a delay of viral rebound. However, ATI trials for the identification of biomarkers remain logistically challenging, particularly in children, necessitating the development of tractable pediatric animal models. While models of ATI in SIV-infected pediatric RMs are not new to the HIV field (38), clinically translatable RM models of ATI using SHIVs have been advancing (39). Thus, we sought to establish an oral SHIV-infected infant model of ATI with a previously validated ART regimen ...
Passive transfer studies using other neutralizing anti-HIV antibodies have generally conformed to our observations with b12 (1, 24, 26,38). Mascola et al. (26), however, did report that the antibody 2G12 and combinations of this antibody with the antibody 2F5 and polyclonal immune IgG (HIVIG) were somewhat more effective in sterile protection against mucosal challenge with the chimeric virus SHIV89.6PD than against intravenous challenge. In particular, those studies showed a surprising efficacy of the antibody 2G12 in mucosal protection. The reasons for this efficacy are unclear, but understanding it is clearly important.. Generally, examination of the literature on passive transfer to naive animals for a wide variety of different viruses and model systems shows that titers of neutralizing antibody in serum around or greater than 1:100 are required for sterile protection (28). For instance, serum neutralizing antibody titers of 1:380 are required to sterilely protect cotton rats against ...
HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments. For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia. Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a
HIV-1 does not persistently infect macaques due in part to restriction by several macaque host factors. This has been partially circumvented by generating chimeric SIV/HIV-1 viruses (SHIVs) that encode SIV antagonist of known restriction factors. However, most SHIVs replicate poorly in macaques unless they are further adapted in culture and/or macaques (adapted SHIVs). Therefore, development of SHIVs encoding HIV-1 sequences derived directly from infected humans without adaptation (unadapted SHIVs) has been challenging. In contrast to the adapted SHIVs, the unadapted SHIVs have lower replication kinetics in macaque lymphocytes and are sensitive to type-1 interferon (IFN). The HIV-1 Envelope (Env) in the chimeric virus determines both the reduced replication and the IFN-sensitivity differences. There is limited information on macaque restriction factors that specifically limit replication of the more biologically relevant, unadapted SHIV variants. In order to identify the IFN-induced host ...
by Tim Horn, Senior Writer & Editor, AIDSmeds.com. HIVs ability to damage the human immune system might amount to an accident of evolution, notably the loss of the protective function of a viral protein called Nef. Like HIV in humans, related strains of simian immunodeficiency virus (SIV) are rampant among many species of monkeys. Unlike HIV in humans, many primates infected with SIV dont experience immune suppression or suffer the symptoms associated with AIDS. The evidence, published by an international team of researchers in the June 2006 issue of Cell, is the first to offer an explanation for this striking difference. The group found that a viral protein known to help the virus evade the immune system, thereby allowing the SIVs that infect monkeys to persist and multiply with high efficiency, also has a protective role in the host immune system. The SIV Nef protein ratchets down the activation of T-cells following infection in primates, thereby limiting the harmful effects that can be ...
Well, Ill try. Yes, it would be ideal to have an animal model, but the problem is that HIV behaves differently in monkeys than it does in men. SIV (Simian Immunodeficiency Virus) is the monkey...
New research suggests that the simian immunodeficiency virus (SIV) lineage was already circulating in monkeys and apes at least 32,000 years ago. During ...
The first in vivo evidence that strains of chimpanzee-carried simian immunodeficiency viruses can infect human cells has been reported by a team of scientists