Disease relevance of nef

• To assess the role of SIV NEF on virus replication and compare its activity with that of its human immunodeficiency virus type 1 counterpart, we examined the activity of an intact nef gene from proviral clone pSIV 102, an isolate from SIV-MAC-251-infected cells [1].
• We examined the ability of a live, attenuated deletion mutant of simian immunodeficiency virus (SIV), SIVmac239Delta3, which is missing nef and vpr genes, to protect against challenge by heterologous strains SHIV89.6p and SIVsmE660 [2].
• Similarly, targeting a cytoplasmic protein, HIV-1 nef, to undergo rapid cytoplasmic degradation induced a greatly enhanced de novo nef-specific CD8+ CTL response in vivo after immunization of mice with either recombinant vaccinia vectors or DNA expression plasmids expressing the degradation targeted nef mutant [3].
• RESULTS: Analysis of multiple viral clones showed nef gene deletions/insertions in 10 out of 15 SP, along with the coexistence of intact and defective nef gene lineages in the same individual over time, whereas these nefgene abnormalities were absent from HIV-1 strains from LTNP [4].
• DESIGN: Genetic and phylogenetic analyses of the V3 region and the nef gene clones over time from uncultured peripheral blood mononuclear cells (PBMC) of American patients with varying HIV disease progression rates [4].

Psychiatry related information on nef

• In previous studies, using polymerase chain reaction amplification of HIV-1 genes directly from pathologic tissues of children who died with AIDS encephalopathy, we showed that the reading frame of the HIV-1 regulatory nef gene is open, suggesting that the nef protein was expressed [5].

High impact information on nef

• (2006) show that the Nef protein from nonpathogenic strains of simian immunodeficiency virus (SIV) induces the downregulation of host T cell receptor/CD3, whereas Nef from human immunodeficiency virus (HIV-1) does not [6].
• Although deletion of nef sequences had no detectable effect on virus replication in cultured cells, deletion of nef sequences dramatically altered the properties of virus in infected rhesus monkeys [7].
• No reversions were observed in the majority of nef sequences analyzed from different time points during infection and from lymphatic tissues at the time of death [8].
• We show that the expression of MHC-I at the surface of lymphoid, monocytic and epithelial cells was reduced in the presence of Nef protein from various HIV-1 strains [9].
• Here we use a Moloney murine leukaemia virus-based retroviral vector in order to express the nef gene of HIV-1 in three lymphocytic cell lines expressing CD4 [10].

Chemical compound and disease context of nef

• The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases [11].
• Chimeric human immunodeficiency virus type 1 virions that contain the simian immunodeficiency virus nef gene are cyclosporin A resistant [12].
• Surprisingly, CyPA-deficient virions remained sensitive to inhibition by CsA, in a manner that depended strongly on the presence of a functional nef gene [13].
• HeLa and Jurkat cell lines carrying the nef gene linked to the CMV promoter or the HIV-1 LTR were isolated by coselection for neomycin resistance [14].
• Genomic Diversity in the Regulatory nef Gene Sequences in Indian Isolates of HIV Type 1: Emergence of a Distinct Subclade and Predicted Implications [15].

Biological context of nef

• Monkeys were infected experimentally with SIV containing difficult-to-revert mutations in nef that selectively eliminated MHC downregulation but not these other activities [16].
• Proviral clone pSIV BA was constructed by introducing a premature termination codon at codon 40 of the nef gene without altering the predicted amino acid sequence of the overlapping env gene [1].
• In addition, it showed that while sequences in the surface portion of the envelope gene determine macrophage tropism, additional sequences derived from the transmembrane portion of envelope and/or nef confer neurovirulence [17].
• Use of the macaque model of human immunodeficiency virus (HIV) pathogenesis has shown that the accessory genes nef and vpu are important in the pathogenicity of simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) [18].
• In pHP, the long terminal repeats (LTRs), the 5' untranslated leader and portions of the env and nef genes were deleted [19].

Anatomical context of nef

• Recent studies from our laboratory demonstrated that SIV replication in primary rhesus macaque astrocyte cultures is dependent upon the nef gene [20].
• The deletion of nef enhanced the formation of syncytia in CD4+ T lymphocytes infected with macrophage-tropic clones, despite a severalfold reduced viral production [21].
• We could not demonstrate an enhanced cell surface expression of HIV-1 envelope in lymphocytes infected with nef-deficient clones to explain the increased syncytium formation [21].
• The nef gene controls syncytium formation in primary human lymphocytes and macrophages infected by HIV type 1 [21].
• The nef protein expressed by vaccinia virus recombinants is phosphorylated by protein kinase C. We investigated the synthesis of the nef protein and its state of phosphorylation during HIV-1 infection of a T4 cell line (CEM cells) [22].

Associations of nef with chemical compounds

• Viral replication was mapped by in situ hybridization for SIV env, gag, and nef RNA, and catecholaminergic varicosities from the ANS were mapped by sucrose phosphate glyoxylic acid chemofluorescence [23].
• Sequencing of the env gene of isolates of SHIV-C strains showed conserved amino acid changes in the Env C2 and V3 regions that included changes to negatively charged amino acids, in the cytoplasmic region of gp41 that included a 42 amino acid deletion, and in the Nef protein [24].
• Serine phosphorylation-independent downregulation of cell-surface CD4 by nef [10].
• The relation between these two proteins was determined by metabolically labeling transfected COS cells and by deleting the initiator methionine of nef [25].
• The high affinity of nefGST for glutathione was exploited to develop an assay to identify cellular proteins capable of interacting with nef [26].

Other interactions of nef

• Functional association between the nef gene product and gag-pol region of HIV-1 [27].

Analytical, diagnostic and therapeutic context of nef

• Sequence analysis revealed a remarkably high level of similarity between their env and nef genes as well as their 3' LTR [28].
• METHODS: Proviral DNA from longitudinally collected uncultured PBMC were subjected to PCR amplification in the nef gene and env V2 and V3 regions, followed by cloning, sequencing and phylogenetic analysis to establish evolutionary relationships between HIV-1 strains over time [4].
• In enhancing the HIV-1 cytopathic effect, the deletion of nef might curtail virus production by infected cells, and thus explain in part the reduced viral load observed in vivo in hosts infected with nef-deficient viruses [21].
• Therefore, during tonsillar SIV Delta nef vaccination, infection is blocked early at the entry portal, which we propose is due in part to innate functions of gamma delta T and dendritic cells [29].
• Thus, lentivirus-mediated shRNA expression targeting the U3-overlapping region of HIV nef represents a feasible approach to genetic vaccine therapy for HIV-1 [30].

References