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Genes, nef (0):
Recent article
Genes, nef
Abstract
Nef is an accessory protein from HIV-1 involved in viral replication, depletion of CD4 + T cells and progression to AIDS. The participation of Nef in altering several of the cellular and subcellular components has been studied in detail. The finding that infected patients over 15 years with HIV-1 va...
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PMID: 19736813
PDF is available here.
PDF is available here.
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Journal of Virology (82)18 2008
Abstract
We longitudinally characterized the rates and extent of HLA-mediated escape and reversion in Gag, Pol, and Nef using a rational definition of HLA-attributable mutation based on the analysis of a large independent subtype B data set. We demonstrate rapid and dramatic HIV evolution in response to immu...
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PMID: 18614631
PDF is available here.
PDF is available here.
Abstract
We investigated the effect of the expression of HIV-1 Nef on the T-cell potential of human hematopoietic CD34(+) precursors. Those progenitors were transduced by using lentiviral vectors expressing Nef and cultured on OP9-DL1 cells allowing the differentiation of T cell from human hematopoietic prec...
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PMID: 18555888
PDF is available here.
PDF is available here.
Abstract
We generated a fusion protein consisting of the host protein cyclophilin A (CypA) linked to the amino terminus of Nef. The resulting CypA-Nef protein enhanced the infectivity of Nef-defective HIV-1 particles and was specifically incorporated into the virions via association with Gag during particle...
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PMID: 18191978
PDF is available here.
PDF is available here.
Journal of Virology (82)6 2008
Abstract
We found that these differences also resulted in differential downregulation by primary simian immunodeficiency virus (SIV) SIV(smm/mac) and HIV-2 Nef alleles. Thus, selective major histocompatibility complex class I downregulation is a conserved mechanism of immune evasion for pathogenic SIV infect...
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PMID: 18199657
PDF is available here.
PDF is available here.
Journal of Microbiology (46)1 2008
Abstract
We verified that most of the Korean isolates belonged to the subtype B, where 78.8% are clustered exclusively of foreign isolates. This cluster has been named the Korean clade subtype B (KCB) in order to distinguish it from other subtype B clusters. Genetic distance analysis suggested that the KCB c...
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PMID: 18337699
PDF is available here.
PDF is available here.
Abstract
We show how the new generation of sequencing technologies, based on high throughput of short reads, can be used to link site variants and reconstruct multiple full strains of the targeted gene, including those of low concentration in the sample. Our algorithm is based on a generative model of the se...
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PMID: 18229680
PDF is available here.
PDF is available here.
Abstract
HIV-associated nephropathy (HIVAN) is a unique form of collapsing focal segmental glomerulosclerosis that typically occurs in patients with advanced HIV disease. The pathogenesis of HIVAN involves direct HIV infection and gene expression in tubular and glomerular epithelial cells; in effect, HIVAN c...
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PMID: 18391591
PDF is available here.
PDF is available here.
Abstract
HIV-associated nephropathy (HIVAN) is a unique form of collapsing focal segmental glomerulosclerosis that typically occurs in patients with advanced HIV disease. The pathogenesis of HIVAN involves direct HIV infection and gene expression in tubular and glomerular epithelial cells; in...
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PMID: 18391591
PDF is available here.
PDF is available here.
Abstract
We show that this serine kinase activity is mediated by members of the novel Protein Kinase C (nPKC) subfamily, PKCdelta and theta. Association with the Nef N-terminus was sufficient to activate PKC leading to phosphorylation of Nef in vitro on a conserved serine residue at position 6. Mutation of s...
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PMID: 17904606
PDF is available here.
PDF is available here.
Abstract
We investigated for the first time the in vitro dimerization properties of spliced HIV-1 RNAs. We found that singly spliced (env, vpr) and multispliced (tat, rev, and nef) RNA fragments are able to dimerize in vitro, and to efficiently form heterodimers with genomic RNA. Chemical probing experiments...
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PMID: 17925344
PDF is available here.
PDF is available here.
Abstract
We studied the central nervous system (CNS) of rhesus macaques during series of vaccination experiments in which attenuated simian immunodeficiency virus (SIV), SIVmac239Deltanef, was applied to the tonsils and the animals were later challenged with pathogenic SIVmac251 or SHIV/89.6P via tonsils or...
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PMID: 17573813
PDF is available here.
PDF is available here.
Abstract
These results will contribute to a better understanding of the pathogenesis of circulating HIV-1 in infected Chinese former blood donors and may have important implications in developing an epitope-based vaccine suitable for Chinese blood donors....
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PMID: 17919112
PDF is available here.
PDF is available here.
Abstract
Though HIV-1 CRF07_BC rapidly spread in China, there have been few reports about this subtype since its first genetic characterization nearly 10 years ago. It was urgent and necessary to know the current gene variation of circulating CRF07_BC strains. Xinjiang was the main region for the CRF07_BC ep...
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PMID: 17725423
PDF is available here.
PDF is available here.
Abstract
: Nef alleles derived from HIV-1-infected children with non-progressive infection were significantly more active in the upregulation of Ii and downregulation of MHC-II than those derived from rapid progressors. CONCLUSION: Nef alleles particularly active in interfering with MHC-II antigen presentatio...
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PMID: 17502720
PDF is available here.
PDF is available here.
Abstract
We provide sequences of 64 gag and 45 nef genes sampled in Malawi, Zambia, Zimbabwe, and South Africa and assess the degree of southern African HIV-1 diversity that will confront these vaccines. Whereas reasonable phylogenetic evidence exists for geographical clustering of subtype C gag and nef sequ...
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PMID: 17411382
PDF is available here.
PDF is available here.
Journal of Virology (81)5 2007
Abstract
We report that CD4 expression levels correlate with inefficient HIV-1 transmission by monocytic cells expressing DC-SIGN. Expression of CD4 on Raji B cells strongly impaired DC-SIGN-mediated HIV-1 transmission to T cells. By contrast, enhanced HIV-1 transmission was observed when CD4 molecules on MD...
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PMID: 17151103
PDF is available here.
PDF is available here.
Abstract
We have cloned 97 nef genes and characterized 10 Nef proteins from autopsy brain and lymphoid tissues from 2 patients with AIDS and HIV-1-associated dementia. Distinct compartmentalization of brain versus lymphoid nef genes was demonstrated within each patient. CD4 and MHC-I downregulation were cons...
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PMID: 16979207
PDF is available here.
PDF is available here.
Vox Sanguinis (92)2 2007
Abstract
Both plasma donors and the haemophiliacs were infected with a subclade of subtype B that is a founder effect lineage in Korea. CONCLUSION: Our data indicate that HIV-1 transmission to 20 haemophiliacs occurred through intravenous injection of Korean-made clotting factor. SUMMARY: A clotting factor m...
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PMID: 17298572
PDF is available here.
PDF is available here.
Abstract
We have sequenced and analyzed HIV-1 subtype C nef sequences from 34 children with rapid (RP) or slow progressing (SP) disease and identified polymorphisms associated with disease stage including motifs involved in specific pathogenic functions. Unlike subtype B, insertions and deletions in the N-te...
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PMID: 17331028
PDF is available here.
PDF is available here.
Abstract
Intriguingly, HIV-lhNef potently inhibited wild-type HIV-1 production in trans. However, HIV-lhNef demonstrated a severe production and replication defect, which we were able to solve by selecting spontaneous virus variants with truncated hairpin structures. Although these escape variants lost the a...
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PMID: 17331227
PDF is available here.
PDF is available here.
Abstract
We show that a single atraumatic application of SIVDeltanef to the tonsils of four rhesus macaques conferred protection against SIVmac251 applied intrarectally 26 weeks later. While this protection was not complete, i.e., challenge virus could be isolated from all immunized animals, it was reflected...
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PMID: 17127448
PDF is available here.
PDF is available here.
Sexual Health (3)4 2006
Abstract
In sequences from nine patients, most of the functional domains of HIV-1 Nef appeared intact, and no major deletions were observed to possibly account for an effect on the delayed disease status. However, the results demonstrate a high incidence of a single amino acid polymorphism (cysteine 138) in...
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PMID: 17112441
PDF is available here.
PDF is available here.
Abstract
We carried out full-length nef gene (approximately 620 bp) sequencing on a large number of clinical isolates of HIV-1 circulating in different geographic regions of India. Comparative and phylogenetic analysis revealed 88% (38/43) of cases was HIV-1 subtype C; four cases were diagnosed as subtype A...
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PMID: 17209762
PDF is available here.
PDF is available here.
Journal of Virology (80)23 2006
Abstract
We report the complete sequence analysis of the provirus harbored in a long-term nonprogressor (patient SG1) 20 years after the first infection with a human immunodeficiency virus type 1 strain lacking nef. The sequencing showed large deletions in the nef-nef and nef-U3 regions. Except for vpu, all...
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PMID: 16987968
PDF is available here.
PDF is available here.
Abstract
Macrophages are recognized as a putative reservoir for HIV-1, but whether HIV can establish latent infection in this cell type is not known. An in vitro model using long-term cultured primary human monocyte-derived macrophages (MDM) infected with an M-tropic, enhanced green fluorescent protein (EGFP)...
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PMID: 16923921
PDF is available here.
PDF is available here.
Journal of Virology (80)21 2006
Abstract
We have examined the functions of nef alleles from six individuals belonging to the same cohort of hemophiliacs infected with HIV-1 prior to 1985 and classified as LTNP in 1995. Three out of six individuals have progressed to HIV disease (late progressors [LP]), whereas the three remainders have mai...
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PMID: 16943296
PDF is available here.
PDF is available here.
Abstract
We characterized nef genes in 10 long-term slow progressors (LTSP) infected with HIV-1 subtype B and 34 control patients. LTSP was defined by the annual decrease in CD4 T cells being less than 20/microl over 10 years in the absence of antiretroviral therapy. They were treated with KRG for a prolonge...
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PMID: 17073619
PDF is available here.
PDF is available here.
Microbes and Infection (8)9-10 2006
Abstract
We developed constitutive and inducible adenovirus vector systems that express high levels of Nef in monocyte-derived dendritic cells (MDDCs). We showed here that Nef expression clearly downregulated CD4 expression of MDDCs but had little or no effect on other surface molecules, including MHC class...
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PMID: 16979362
PDF is available here.
PDF is available here.
HIV Medicine (7)2 2006
Abstract
nef sequence variations may not be common in perinatally infected African children. Further studies are warranted in HIV-1-infected subjects in settings where infection is endemic....
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PMID: 16420252
PDF is available here.
PDF is available here.
Abstract
We studied the impact of the CD4 downregulation function of Nef on its pathogenesis in vivo, in the absence of viral replication, in the CD4C/HIV transgenic (Tg) mouse model. Two independent Nef mutants (RD35/36AA and D174K), known to abrogate CD4 downregulation, were tested in Tg mice. Flow cytomet...
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PMID: 16310238
PDF is available here.
PDF is available here.
FASEB Journal (20)3 2006
Abstract
We report that species-adapted nucleofection procedures combined with optimized cultivation conditions render proliferating primary T cells, B cells, and natural killer cells from widely used rat and mouse strains susceptible to high-level gene delivery. As a result, transgene expression levels were...
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PMID: 16401643
PDF is available here.
PDF is available here.
Journal of Virology (80)6 2006
Abstract
We performed mutational analysis of three primary HIV-1 Nef clones that exhibited similar capacities for downregulation of CD4 and MHC-I but variable abilities to associate with activated Pak2. Our results demonstrate that Nef amino acids at positions 85, 89, 187, 188, and 191 (L, H, S, R, and F in...
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PMID: 16501114
PDF is available here.
PDF is available here.
Abstract
We present the phylogenetic analysis of one nonautochthonous and four autochthonous (including a near full-length genome) Brazilian HIV-1 subtype D strains identified in Rio de Janeiro State, where subtypes B, F1, and BF1 recombinants predominate. Phylogenetic inferences using maximum likelihood wer...
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PMID: 16478405
PDF is available here.
PDF is available here.
Abstract
We have shown that HIV-1 nef double-stranded RNA from AIDS patients who are long-term nonprogressors, inhibits HIV-1 transcription; and that nef-derived miRNA, miR-N367, is produced in human T-cells persistently infected with HIV-1. The miR-N367 can block HIV-1 Nef expression and long terminal repea...
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PMID: 16957380
PDF is available here.
PDF is available here.
Abstract
We utilized the simian immunodeficiency virus model of AIDS to examine evolution of nef gene in gut-associated lymphoid tissue (GALT) during primary and early asymptomatic stages of infection. Macaques were infected with a cloned virus, SIVmac239/nef-stop harboring a premature stop codon in the nef...
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PMID: 16168456
PDF is available here.
PDF is available here.
Abstract
We conclude that Nef induces the early molecular changes in podocytes that are essential for the dedifferentiation and proliferation of podocytes in HIVAN pathogenesis. These data provide the first clear molecular evidence that Nef alters the podocyte phenotype in vivo....
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PMID: 16260903
PDF is available here.
PDF is available here.
Journal of Immunology (175)10 2005
Abstract
We established a panel of transfectants of the murine DC line, DC2.4, stably expressing differing levels of either wild-type Nef, or a number of Nef mutants lacking key functional motifs. Transfectants expressing increasing levels of wild-type Nef demonstrated a dose-dependent shrinkage and loss of...
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PMID: 16272310
PDF is available here.
PDF is available here.
Journal of Immunology (175)10 2005
Abstract
CD8+ T lymphocyte responses play an important role in controlling HIV-1 replication but escape from CD8+ T cell surveillance may limit the effectiveness of these responses. Mother-to-child transmission of CD8+ T cell escape variants may particularly affect CD8+ T cell recognition of infant HIV-1 epi...
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PMID: 16272358
PDF is available here.
PDF is available here.
Abstract
We inactivated the T-rich region, the Polypurine tract and attachment (att) sequences in nef by silent mutations and inserted intact cis-regulatory elements just upstream of the core enhancer. These modifications severely truncated the U3 region and eliminated the nef overlap. The resulting HIV-1 mu...
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PMID: 16102792
PDF is available here.
PDF is available here.
Abstract
We here report the first phylogenetic and putative amino acid sequence variability analyses of nef accessory gene. Viral sequences (n = 53) were amplified by nested PCR from proviral DNA purified from peripheral blood mononuclear cells of HIV-1 infected individuals (n = 49). Phylogenetic inference a...
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PMID: 16032733
PDF is available here.
PDF is available here.
Molecular Biotechnology (31)1 2005
Abstract
We have constructed reading frames for the HIV-1 YU-2 minor proteins Vpr, Vpu, Vif and Nef that are codon-optimized for high-level expression in mammalian cells. We show that, in the absence of the Rev/Rev-response element system, these codon-optimized reading frames result in greatly increased leve...
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PMID: 16118417
PDF is available here.
PDF is available here.
Journal of Virology (79)18 2005
Abstract
We report a comprehensive genetic analysis of an HIV-1 superinfection acquired heterosexually. The infected individual was in a high-risk cohort in Tanzania, was exposed to multiple subtypes, and was systematically evaluated every 3 months with a fluorescent multi-region genotyping assay. The subjec...
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PMID: 16140747
PDF is available here.
PDF is available here.
Abstract
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% r...
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PMID: 16043695
PDF is available here.
PDF is available here.
Journal of Virology (79)16 2005
Abstract
We demonstrate that, similarly to the SIVmac239 nef, primary SIVsm and HIV-2 nef alleles down-modulate cell surface expression of human CD4, CD28, CD3, and class I or II major histocompatibility complex (MHC-I or MHC-II, respectively) molecules, up-regulate surface expression of the invariant chain...
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PMID: 16051847
PDF is available here.
PDF is available here.
Abstract
We assessed the ability of Nef to alter the cell surface expression of human CD1d. In cells co-expressing CD1d and Nef, a substantial reduction in the cell surface level of CD1d was observed, with a concomitant reduction in the activation of CD1d-restricted NKT cells. Nef had a minimal effect on the...
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PMID: 15916790
PDF is available here.
PDF is available here.
Abstract
We identified an unusual case of human immunodeficiency virus type 1 (HIV-1) infection in a patient (GM43) who exhibited a persistently low antibody response and undetectable viral load during a 5-year follow-up period. GM43 harbored HIV-1 circulating recombinant form 01_AE with gross deletions in t...
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PMID: 15942894
PDF is available here.
PDF is available here.
Journal of Immunology (174)12 2005
Abstract
We examined potential correlates of delayed HIV disease progression in 51 HIV-1-infected African children. Children were assigned to progression subgroups based on clinical characterization. HIV-1-specific immune responses were studied using a combination of ELISPOT assays, tetramer staining, and FA...
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PMID: 15944328
PDF is available here.
PDF is available here.
Abstract
Journal of Virology (79)10 2005
Abstract
We studied a murine model of AIDS, the CD4C/HIV transgenic (Tg) mouse model, to assess the importance of the apoptotic pathway in human immunodeficiency virus type 1 (HIV-1) pathogenesis. In these Tg mice, Nef is the major determinant of the disease and is expressed in immature and mature CD4(+) T c...
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PMID: 15858021
PDF is available here.
PDF is available here.
Cancer Research (65)8 2005
Abstract
We analyzed the possibility of developing virotherapy for T-cell acute lymphoblastic leukemia. Virotherapy is based on the exclusive replication of a virus in leukemic cells, leading to the selective removal of these malignant cells. We constructed a minimized derivative of HIV-1, a complex lentivir...
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PMID: 15833868
PDF is available here.
PDF is available here.
Current HIV Research (3)2 2005
Abstract
The transmission of HIV and the progression of HIV disease are influenced not only by a large number of human host factors, but also by certain correlates of the ever fluctuating virus quasispecies. The present review article aims at providing the current state of knowledge as well as an in-depth cr...
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PMID: 15853718
PDF is available here.
PDF is available here.
Journal of Virology (79)8 2005
Abstract
We demonstrate that macrophage tropism is not sufficient for replication in astrocytes and that specific amino acids in the transmembrane (TM) portion of Env are also important for optimal SIV replication in astrocytes. Specifically, a Gly at amino acid position 751 and truncation of the cytoplasmic...
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PMID: 15795280
PDF is available here.
PDF is available here.
Journal of Virology (79)8 2005
Abstract
We intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239D...
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PMID: 15795274
PDF is available here.
PDF is available here.
Journal of Virology (79)5 2005
Abstract
We have previously shown that human immunodeficiency virus type 1 (HIV-1) virions which have their own nef gene deleted and are trans complemented to contain HIV-2 or simian immunodeficiency virus (SIV) Nef become resistant to treatment with cyclosporin A. To expand and confirm these studies, we hav...
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PMID: 15709044
PDF is available here.
PDF is available here.
Journal of Virology (79)3 2005
Abstract
We assessed the ability of rat, mouse, and hamster cells to support key effector functions of Nef. In cell lines from rodents, the subcellular distribution of wild-type HIV type 1 strain SF2 Nef and mutants was comparable to that in human cells. Nef downregulated human CD4 from the cell surface, was...
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PMID: 15650191
PDF is available here.
PDF is available here.
Abstract
We synthesised DNA vaccine constructs that encode consensus HIV-1 subtype C Tat, Rev and Nef proteins. Proteins carrying inactivating mutations were tested for functional activity and highly expressing, inactive Tat, Rev and Nef mutants were identified and their reading frames fused into a TatRevNef...
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PMID: 15629359
PDF is available here.
PDF is available here.
Microbiology and Immunology (49)12 2005
Abstract
We previously reported that a nef-deleted SHIV (SHIV-NI) is nonpathogenic and gave macaques protection from challenge infection with pathogenic SHIV-C2/1. To investigate whether IFN-gamma augments the immune response induced by this vaccination, we examined the antiviral and adjuvant effect of recom...
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PMID: 16365534
PDF is available here.
PDF is available here.
Journal of Infectious Diseases (190)12 2004
Abstract
We studied the evolution and compartmentalization of nef/long terminal repeat (nef/LTR)-deleted human immunodeficiency virus type 1 (HIV-1) from a long-term survivor who developed HIV-associated dementia (HIVD). Analysis of sequential blood-derived HIV-1 isolated before and during HIVD revealed a pe...
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PMID: 15551218
PDF is available here.
PDF is available here.
Zhonghua Yixue Zazhi (84)23 2004
Abstract
The strength of HIV-1 nef specific CD8(+) T cell responses of LTNP group was 404 +/- 33 SFC/10(6) PBMCs, significantly higher than that of the AIDS group (59 +/- 121 SFC/10(6) PBMCs). The strength of HIV-1 nef specific CD8(+) T cell responses was positively correlated with the CD4(+) T cell count. N...
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PMID: 15730808
PDF is available here.
PDF is available here.