Disease relevance of vif

• Three other viral genes, vif, vpu, and vpr, affect the assembly and replication capacity of newly made virus particles [1].
• Rev activates expression of the human immunodeficiency virus type 1 vif and vpr gene products [2].
• Interestingly, these processing intermediates, like Vif, associated with viral nucleoprotein complexes more rigidly than mature capsid and NC [3].
• High level expression of human immunodeficiency virus type-1 Vif inhibits viral infectivity by modulating proteolytic processing of the Gag precursor at the p2/nucleocapsid processing site [3].

Recombinant SIVcpz-gab/HIV-1 group M isolate

A highly divergent HIV-1 isolate, designated YBF 30, was obtained in 1995 from a 40-year-old Cameroonian woman with AIDS. Depending on the genes studied, phylogenetic analysis showed that YBF30 branched either with SIVcpz-gab or between SIVcpz-gab and HIV-1 group M. The structural genes and tat, vpr, and nef of YBF30 are approximately equidistant from those of HIV-1 group M and SIVcpz-gab. In contrast, vif and rev are closer to HIV-1 group M, and vpu is highly divergent [4].

High impact information on vif

• The HIV-1 accessory protein Vif (virion infectivity factor) is required for the production of infectious virions by CD4(+) lymphocytes [5].
• The Vif gene of HIV-1 blocks this host restriction and so allows virus replication [6].
• HIV-1 Vif seems to be required during the late stages of virus production for the suppression of an innate antiviral phenotype that resides in human T lymphocytes [7].
• Thus, in the absence of Vif, expression of this phenotype renders progeny virions non-infectious [7].
• Furthermore, in cells the HP68-Gag complex is associated with HIV-1 Vif, which is involved in virion morphogenesis and infectivity [8].

Chemical compound and disease context of vif

• To test this hypothesis, we produced pseudotyped wild-type and vif-deleted HIV gpt virions (which contain the HIV-1 genome with the bacterial mycophenolic acid resistance gene gpt in place of the viral env gene) in permissive cells, and we used them to generate nonpermissive H9 leukemic T cells that express these proviruses [9].
• Mutation of Ser144 to alanine resulted in loss of Vif activity and >90% inhibition of HIV-1 replication [10].
• These studies suggest that phosphorylation of Vif by a serine/threonine protein kinase(s) plays an important role in regulating HIV-1 replication and infectivity [10].
• Formation of infectious human immunodeficiency virus type 1 (HIV-1) requires suppression of multiple cytidine deaminases by Vif [11].
• In sucrose density gradients, Vif cosediments with capsid proteins even after detergent treatment of virus preparations, suggesting that Vif is associated with the inner core of HIV particles [12].

Biological context of vif

• However, elimination of the vif and vpr accessory genes together, but not individually, renders the virus incapable of causing cell death and G(2) cell cycle blockade [13].
• The entire vpu gene as well as the 5' half of the vif gene were codon optimized and the resulting open reading frames (ORFs) (vphu and hvif, respectively) were cloned in autonomous expression vectors under the transcriptional control of the CMV promoter [14].
• DNA sequence analysis of PCR-amplified products revealed a total of 5 nucleotide changes in the LTR while vif had 2 consensus amino acid changes [15].
• The gag, vif, and vpx had no consensus amino acid substitutions, whereas vpr had 1 consensus substitution [15].
• Single point mutation of M1 within an infectious molecular clone is detrimental for HIV-1 exon 2 recognition without affecting Rev-dependent vif expression [16].

Anatomical context of vif

• We thus identify vif and vpr as necessary for T cell cytopathic effects induced by HIV-1 [13].
• The vif gene of human immunodeficiency virus type 1 (HIV-1) encodes a basic Mr 23,000 protein that is necessary for production of infectious virions by nonpermissive cells (human lymphocytes and macrophages) but not by permissive cells such as HeLa-CD4 [9].
• These studies showed that vif is also essential for the initiation of productive HIV-1 infection in primary monocyte/macrophage cultures after cell-free virus transmission [17].
• Additional purification using a continuous density gradient indicated that the majority of the membrane-bound Vif copurifies with the plasma membrane [18].
• The association of Vif with vimentin can cause the collapse of the intermediate filament network into a perinuclear aggregate [12].

Associations of vif with chemical compounds

• In vivo studies demonstrated that Vif is highly phosphorylated on serine and threonine residues [10].
• For vif sequences, NT-2 contained stop codons and no initiation codons, whereas NT-1 sequences carried a substitution of a highly conserved tyrosine to histidine at position 30 [19].
• A large number of scanning missense (mostly alanine substitution) and deletion mutations were introduced into the HIV-1HXB3 vif gene, and the resulting proteins were evaluated for the induction of virus infectivity as well as subcellular localization [20].
• We found a novel GPGGMI motif in the V3 loop, a novel insertion of a proline in the C3 region, and persistent deletion of two amino acids in the vif gene [21].
• Not surprisingly, on a vif background nascent minus strand DNA can be extensively edited leaving multiple uracil residues [22].

Physical interactions of vif

• Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression [14].

Other interactions of vif

• RESULTS: DNA vaccine construct (pVVN-P) expressing Vif, Vpu and Nef was processed and the fusion protein was cleaved appropriately [23].
• We constructed an RNase P and tRNase ZL-associated vif and tat sEGS expression vector; which used the RNA-polymerase III dependent U6 promoter, as an expression cassette for EGS [24].
• The data presented herein show that the HIV-1 primed CD4(+) T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4(+) T cells [25].
• Interaction of human immunodeficiency virus type 1 Vif with Gag and Gag-Pol precursors: co-encapsidation and interference with viral protease-mediated Gag processing [26].

Analytical, diagnostic and therapeutic context of vif

• By Western blot analysis, viral structural proteins expressed after transfection of RD cells by wild-type or vif mutant proviruses were indistinguishable [27].
• To identify the phosphorylation sites, 32P-labeled Vif was digested by V8 protease and the peptides were resolved by reverse-phase high performance liquid chromatography [10].
• Double-label immunofluorescence analyses of cells productively infected with HIV-1 or feline immunodeficiency virus revealed dramatic patterns of colocalization between Vif and the virally encoded Gag proteins [18].
• Using HIV infectivity, virion incorporation, immunoprecipitation, and in vitro ubiquitin conjugation assays, we show that the ability of Vif to inhibit antiviral activity of APOBEC3 proteins positively correlates with its ability to bind and ubiquitinate these proteins by a Vif-Cullin5-ElonginB-ElonginC (Vif-BC-Cul5) complex [28].
• Direct sequencing of vif amplified by PCR from uncultured lymphocytes of 15 individuals at various stages of progression toward AIDS demonstrated vif open reading frames in 13 of 15 samples tested [29].

References