Investigators have identified functional and structural nef gene defects that occur in HIV-infected paediatric patients with a non- or slow- progressing form of the disease, according to a report published in the November 20th issue of AIDS Research and Human Retroviruses. Dr. Rebeca Geffin, from the University of Miami School of Medicine, and colleagues analysed the structure and function of HIV-1 nef genes in seven children who were perinatally infected with the virus. Of this group, four patients were long-term nonprogressors, one was a slow progressor, and two were rapid progressors. Of the five slow progressors or nonprogressors, only one patient had large deletions of the nef gene, the authors note. The other four had nef genes of normal size but with a higher frequency of discrete changes than the genes of rapid progressors.. On functional analysis, the majority of Nef proteins derived from the study group were capable of binding…kinase p62, indicating that this function is well ...

Elite controllers or suppressors (ES) are HIV-1 infected patients who maintain viral loads of | 50 copies/ml without antiretroviral therapy. CD8+ T cells are thought to play a key role in the control of viral replication and exert selective pressure on gag and nef in HLA-B*57 positive ES. We previously showed evolution in the gag gene of ES which surprisingly was mostly due to synonymous mutations rather than non-synonymous mutation in targeted CTL epitopes. This finding could be the result of structural constraints on Gag, and we therefore examined the less conserved nef gene. We found slow evolution of nef in plasma virus in some ES. This evolution is mostly due to synonymous mutations and occurs at a rate similar to that seen in the gag gene in the same patients. The results provide further evidence of ongoing viral replication in ES and suggest that the nef and gag genes in these patients respond similarly to selective pressure from the host.

Hi everybody? Have any of you managed to get Finder to display the thumbnails it generates in Icon mode (CMND+1) to respect their modified...

The replication competence of human immunodeficiency virus type 1 genomes containing mutations in the nef open reading frame was evaluated in continuous cell lines. Mutants that contained a deletion in the nef open reading frame, premature termination codons, or missense mutations in the N-terminal myristoylation signal were constructed. The replication of these mutants was tested in three ways. First, plasmid genomes were used to transfect T-lymphoblastoid cells. Second, low-passage posttransfection supernatants were used to infect cells with a relatively low virus input. Third, high-titer virus stocks were used to infect cells with a relatively high virus input. These experiments demonstrated a 100- to 10,000-fold decrement in p24 production by the nef mutants compared with that by the wild-type virus. The greatest difference was obtained after infection with the lowest virus input. The myristoylation signal was critical for this positive effect of nef. To investigate the mechanism of the ...

Maximum likelihood analysis of positive selection in the HIV-1 nef gene: We first reconstructed maximum likelihood trees for samples from within the hemophiliac patient, taking each time point separately and in combination. Three codon-based maximum likelihood models were then applied to see which provided the best fit to these data. Since the positive selection model has two more parameters than the neutral model, the models are nested and their likelihoods can be compared directly using a χ2-test with d.f. = 2. As can be seen in Table 1, the positive selection model has a better fit to the data at 25 mo (P , 0.001), with 20.9% falling into the selected category (ω3 = 8.126). Although positive selection was not significantly favored at 41 mo postinfection (0.1 , P , 0.05), a high value of ω3 (2.671) was obtained for 22.7% of the sites. There was no evidence for positive selection at 11 mo. When successive data points were combined (i.e., 11 plus 25 mo and 25 plus 41 mo) the positive ...

We studied the mechanisms underlying the down‐regulation of CD28 expression on the cell surface by HIV‐1 and SIV Nef proteins. Genetic and functional evidence from our studies indicates that Nef induces CD28 endocytosis via an AP‐2 clathrin adaptor‐dependent pathway, and that this is mediated by direct interactions between Nef, AP‐2 and CD28.. Nef probably makes direct contacts with the membrane‐proximal region in the CD28 cytoplasmic domain. This is suggested by the observation that induction of CD28 endocytosis by SIV and HIV‐1 Nef proteins requires partially overlapping but distinct sets of amino acid residues in the membrane‐proximal region of the CD28 cytoplasmic domain. The use of different target sites in the CD28 cytoplasmic domain by HIV‐1 and SIV Nef proteins argues against the possibility that they bind CD28 via a common bridging protein and implies that they contact the CD28 cytoplasmic domain directly.. Previous data indicate that Nef‐induced endocytosis of CD4 ...

The report, Subverting Safer Finance by think-tank nef (the new economics foundation), reveals that compared with other major financial centres, including the US, the UK is part of the problem in key areas of financial reform, rather than leading the search for solutions.. In the UK, we are presented with the idea that we cannot act alone on financial reform and other nations stand in the way of global financial stability. We ask whether the reverse might be the case, and the UK itself is a haven that threatens the stability of the global economy. We call for the UK to live up to its image as a pre-eminent global financial centre and demonstrate strong international leadership on better regulation instead of pandering to vested financial interests. nef found that in areas including potentially damaging speculation in food, energy and minerals, the Alternative Investment Market, naked short-selling and British tax havens, the UK is holding back urgently needed regulation.. ...

Abcam provides specific protocols for Anti-HIV1 Nef antibody [3F2] (ab25866) : Western blot protocols, Immunoprecipitation protocols

Listen to DaBoyDame, Blac Youngsta & Mozzy featuring Nef The Pharaoh Look At Me Now. DaBoyDame linked up with two of the biggest street rappers, Blac Young...

Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocytes function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells.

Biochemical and cell-based studies indicate that Nef has multiple functions and that these functions are performed through multiple independent interactions with the host cell signal transduction and protein sorting machinery (29, 36, 45). This study indicates that a 239-Nef mutation which disrupts the interactions of Nef required for the downregulation of CD4 expression and for enhanced SIV replication in vitro also disrupts SIV replication in rhesus macaques. Not only were viral loads low early in macaques infected with the SIV containing the 239(EDR)-Nef variant, but there was also a strong selective pressure for revertants and second-site mutations which restored Nef function. The selection of these changes was associated with rises in viral loads, and virus recovered from these animals possessed virologic properties similar to those of wild-type SIV. While the EDR mutation disrupts other Nef functions, such as downregulation of CD28 cell surface expression (T. Swigut and J. Skowronski, ...

Daniel et al., 1992: Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC. Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science (New York, N.Y.). 1992; 258(5090); 1938-1941. [PubMed: 1470917 ...

HIV-1 isolate R3A Nef mutants G2, WL58, RR106, LL165, E160NNSLL165, and DD175 fail to induce release of IFN-alpha in pDCs, suggesting that the Nef function responsible for CD4 downregulation is crucial for pDCs stimulation by ...

I remember a long while ago i told nef that they would make a great mentor and i still fully believe they would be a great purple mouse! Ive been in lots of shifts with nef and they are always great to see and talk to in a shift, they are friendly and kind when they interact with different people and also in discord its the same, i always see them talking with people and trying to help if someone has a problem or questions. in terms of knowledge i see them play a lot of sec and other jobs so i feel they definitely have lots of experience in many jobs and enough to be able to help lots of people! at the jobs they do they do very well too like sec, having nef on the team is always great and fun! maybe nef hos one day hehe ...

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Hello Everyone! I am considering building up a short carbine as a walking-around gun, based upon a new, steel-receiver H&R/NEF Handi-Rifle. The barrel...

HIV patients are at a greater risk of developing atherosclerosis than non-infected individuals, partly due to the impairment of the ATP-Binding Cassette A1 (ABCA1) cholesterol transporter by the HIV-1 viral protein Nef leading to accumulation of cholesterol inside the cell. While studying the possible mechanism of Nef-mediated disruption of cholesterol efflux, we found that ABCA1 interacts with Nef, but a direct interaction with Nef is dispensable for the inactivation of ABCA1. Using mass spectroscopy we identified calnexin as a protein that associates with both ABCA1 and Nef and provided evidence to show that in the presence of Nef, ABCA1-calnexin interaction is disrupted leading to ABCA1 retention in the ER, subsequent degradation and impairment of cholesterol efflux. However, the molecular interactions taking place remained unknown as Nef is not known to enter the ER lumen and the domain of calnexin involved in binding to substrate proteins is located within the ER lumen. We hypothesized that ...

In seltenen Fällen kann auch ein Antikörper gegen die C3-Konvertase des klassischen Weges-(C4bC2b) nachgewiesen werden. Ebenfalls sehr selten kann man Autoantikörper gegen C3 oder Nicht-C3Nef Autoantikörper gegen andere Bestandteile der C3-Konvertase nachweisen. Wegen der Seltenheit bleibt die Interpretation dieser Befunde in der Nephrologie problematisch.. ...

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 ...

A defining characteristic of HIV-1 infection is the ability of the virus to persist within the host. Specifically, MHC-I downregulation by the HIV-1 accessory protein Nef is of critical importance in preventing infected cells from cytotoxic T-cell mediated killing. Nef downregulates MHC-I by modulating the host membrane trafficking machinery, resulting in the endocytosis and eventual sequestration of MHC-I within the cell. In the current report, we utilized the intracellular protein-protein interaction reporter system, bimolecular fluorescence complementation (BiFC), in combination with super-resolution microscopy, to track the Nef/MHC-I interaction and determine its subcellular localization in cells. We demonstrate that this interaction occurs upon Nef binding the MHC-I cytoplasmic tail early during endocytosis in a Rab5-positive endosome. Disruption of early endosome regulation inhibited Nef-dependent MHC-I downregulation, demonstrating that Nef hijacks the early endosome to sequester MHC-I within the

Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut ...

ATCC® Genuine Nucleics can be used for assay development, verification, validation, monitoring of day-to-day test variation and lot-to-lot performance of molecular-based assays. The quantitative format allows for the generation of a standard curve for quantitative PCR (qPCR) to determine viral load and for other molecular biology applications. Preparation includes fragments from the 5 LTR, gag gene, pol gene (including protease, reverse transcriptase, and integrase regions), tat gene, rev gene, and nef gene. This construct also includes clinically significant mutation profiles to allow compatibility with the CDC genotyping assay patent, including 41L, 67N, 70R, 103N, 181C, 215Y, and 90M.

Jülich, 4 August 2017 - Around 37 million people around the globe are living with HIV. The illness associated with the infection, acquired immune deficiency syndrome (AIDS), can currently be treated with drugs - but is not yet curable. The human immunodeficiency virus (HIV) thus remains one of the greatest challenges for the public health system. The viral NEF (negative factor) protein is viewed as an important virulence factor contributing decisively to the course of the disease. Scientists at Jülichs Institute of Complex Systems and at the Düsseldorf Institut für Physikalische Biologie have now discovered that NEF requires a certain interaction partner in order to reach the plasma membrane of the host cell: the GABA(A) receptor-associated protein (GABARAP). When the researchers switch off this protein, NEF no longer reaches the inside of the plasma membrane. The article published in the journal Scientific Reports contributes to a better understanding of the functions of both the viral and human

HIV-1 Nef is normally an essential pathogenic aspect for HIV/AIDS pathogenesis. needed the membrane layer concentrating on function of Nef and was cell density-dependent. After that, we demonstrated that Nef transfer was cell-cell contact-dependent, as publicity to lifestyle supernatants or exosomes from HIV-infected Jurkat or Nef-expressing Jurkat and 293T led to small Nef recognition in […]. ...

Staropoli I, Dufloo J, Ducher A, Commere PH, Sartori-Rupp A, Novault S, Bruel T, Lorin V, Mouquet H, Schwartz O and Casartelli N. J Virol. 2019. doi:10.1128/JVI.01783-19 ABSTRACT

A class of antibiotic molecules called pleicomacrolides inhibit the Nef protein, which HIV uses to evade the bodys immune system.

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

HIV-1 Nef critically contributes to AIDS in part by augmenting virus titers in infected individuals. Analyzing which of Nefs activities contribute to HIV pathogenesis has been hampered by the lack of a cell culture model in which Nef exerts pronounced effects on HIV replication. The human lymphoid aggregate culture (HLAC) from tonsil maintains the cell populations and cytokine milieu found in vivo, supports a productive infection without exogenous stimulation, and Nef contributes to efficient HIV-1 replication as well as CD4+ T cell depletion in this experimental ex vivo-model. To identify determinants in Nef that mediate these activities, we infected HLAC with a panel of isogenic HIV-1NL4-3 strains that encode for well-characterized mutants of HIV-1SF2 Nef. Determination of HIV-1 replication revealed that enhancement of the virus spread by Nef is governed by a complex set of protein interaction surfaces. In contrast, increased CD4+ T lymphocyte depletion depended on only two protein interaction

P27 (Negative Regulatory Factor or Nef) - Drugs in Development, 2021 provides in depth analysis on P27 (Negative Regulatory Factor or Nef) targeted pipeline therapeutics. The report provides comprehensive information complete with Analysis by Indications, Stage of Development, Mechanism of Action (MoA), Route of Administration (RoA) and Molecule Type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in P27 (Negative Regulatory Factor or Nef) targeted therapeutics development and features dormant and discontinued projects. The report analyses the pipeline products across relevant therapy areas under development targeting P27 (Negative Regulatory Factor or Nef).. The report helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to ...

In recent years, multiple circulating recombinant forms (CRFs) and unique recombinant forms of human immunodeficiency virus type 1 (HIV-1) have been described in Yunnan, China. Here, we identified a novel HIV-1 CRF (CRF86_BC) isolated from three heterosexuals with no obvious epidemiologic linkage in western Yunnan (Baoshan prefecture) in China. CRF86_BC had a subtype C backbone with four subtype B fragments inserted into the pol, vpr, vpu, env, and nef gene regions, respectively. Furthermore, subregion tree analysis revealed that subtype C backbone originated from an Indian C lineage and subtype B segment inserted was from a Thai B lineage. They are different from previously documented B/C forms in its distinct backbone, inserted fragment size, and break points. This highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in this region.. ...

The HIV-1 Nef protein is a pathogenic factor modulating the behavior of infected cells. Nef induces actin cytoskeleton changes and impairs cell migration

Peng, B.; Voltan, R.; Cristillo, A.D.; Alvord, W.Gregory.; Davis-Warren, A.; Zhou, Q.; Murthy, K.K.; Robert-Guroff, M., 2006: Replicating Ad-recombinants encoding non-myristoylated rather than wild-type HIV Nef elicit enhanced cellular immunity

The Northern Elders Forum, NEF, has described the disbandment of the Special Anti-Robbery Squad, SARS, a unit of the Nigeria Police Force

The multifunctional Nef protein of HIV-1 is important for the progression to AIDS. One action of Nef is to down-regulate surface MHC I molecules, helping infected cells to evade immunity. We found that Nef also down-regulates the macrophage-expressed MHC 1b protein HFE, which regulates iron homeostasis and is mutated in the iron-overloading disorder hemochromatosis. In model cell lines, Nef reroutes HFE to a perinuclear structure that overlaps the trans-Golgi network, causing a 90% reduction of surface HFE. This activity requires a Src-kinase-binding proline-rich domain of Nef and a conserved tyrosine-based motif in the cytoplasmic tail of HFE. HIV-1 infection of ex vivo macrophages similarly down-regulates naturally expressed surface HFE in a Nef-dependent manner. The effect of Nef expression on cellular iron was explored; iron and ferritin accumulation were increased in HIV-1-infected ex vivo macrophages expressing wild-type HFE, but this effect was lost with Nef-deleted HIV-1 or when infecting

Dendritic cells (DCs) are thought to play a crucial role in the pathogenesis of HIV-1 infection. DCs are believed to transport virus particles to lymph nodes before transfer to CD4(+) lymphocytes. We have investigated the role of Nef in these processes. HIV-1 replication was examined in human immature DC-lymphocyte cocultures and in DCs or lymphocytes separately. Using various R5-tropic and X4-tropic HIV-1 strains and their nef-deleted (Deltanef) counterparts, we show that Nef is required for optimal viral replication in immature DC-T cells clusters and in T lymphocytes. Nef exerts only a marginal role on viral replication in immature DCs alone as well as on virion capture by DCs, long-term intracellular accumulation and transmission of X4 strains to lymphocytes. We also show that wild-type and Deltanef virions are similarly processed for MHC-I restricted exogenous presentation by DCs. Taken together, these results help explain how HIV-1 Nef may affect viral spread and immune responses in the infected

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 ...

Optimal HIV-1 infectivity requires the presence of both the viral factor Nef and the cellular protein cyclophilin A (CyPA) during virion assembly. These two proteins are integral components of HIV-1 particles. Both CyPA and Nef facilitate a step in the viral life cycle occurring between penetration …

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 ...

HIV-1 is known to aggravate HCV-related liver disease by accelerating HCV replication through as yet unclear mechanisms. Recent studies indicate that HIV-1 Nef...

Since you allude to my post I will respond. You are incorrect that most Mossberg accessories will not fit the Maverick. Sans the fore grip, safety, and trigger housing all else does IIRC. In fact the heatshield, buttstocks, sidesaddles, scope mounts, slings, barrels, most internal parts, beads, and pistol grips are direct interchange parts. I have seen some Mavericks from the factory with Mossberg style forearms. Also some 590 parts will not fit on a 500 with out major modifications. Barrels and mag tubes are two such parts ...

An additional series of mutational analyses revealed a fine specificity for the lipopeptide recognition by the T cells. The 5-mer Nef peptide conjugated with a shorter (C10) saturated fatty acid (C10-GGAIS) showed reduced T cell stimulation activity compared with C14nef5, and no T cell response was detected for C6-GGAIS (Fig. 1F), further confirming that the peptide modification with a fatty acid of the C14 chain length (myristic acid) was essential for activation of the 2N5.1 cells. The N-terminal amino acid sequence (GGAIS) of the Nef protein matches with a typical N-myristoylation motif, Gly-X-X-X-(Ser/Thr), in which X is any amino acid (3). Whereas the serine-to-threonine substitution (C14-GGAIT) did not affect the antigenic activity, alanine substitution for either the second glycine residue (C14-GAAIS) or the isoleucine residue (C14-GGAAS) located between the conserved flanking amino acid residues totally abrogated the activity (Fig. 1F). Furthermore, addition of an amide linkage to the ...

University of Leeds Astbury Centre of Structural Molecular Biology and Division of Microbiology Research Fellowship in Structural Biology/Virology Closing date: 4 February 2000 The following positions are available within an expanding research group that is investigating the molecular basis of viral pathogenesis, particularly in relation to hepatitis C virus and HIV. Research Fellow: The structural and functional role of co- and post-translational modifications at the N-terminus of the HIV-1 Nef protein funded by the BBSRC for a period of 3 years from June 2000. Nef is a myristoylated phosphoprotein that is critical for viral pathogenesis. Whilst some structural information about the protein is available the influence of both myristoylation and phosphorylation on the structure of the native protein is unclear. You will therefore undertake structural studies on the native, myristoylated Nef protein expressed either using baculovirus or E.coli systems. This is a joint project between the ...

In a phase I/IIa clinical trial, 17 HIV-1 infected patients, stable on cART, received 4 vaccinations with autologous dendritic cells electroporated with mRNA encoding Tat, Rev and Nef, after which cART was interrupted. Vaccination was safe and feasible. During the analytical treatment interruption ( …

The Presidency has launched a scathing attack on the Northern Elders Forum (NEF), insisting that the organisation is a General without a troop. Recall