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Gene Products, vif (1):
Recent article
Gene Products, vif
Journal of Virology (84)16 2010
Abstract
We report that this is generally not the case: some lentiviral Vif proteins are capable of triggering the degradation of both the A3Z3-type protein of their normal host species and those of several other mammals. For instance, SIV(mac) Vif can mediate the degradation of the human, macaque, and cow A...
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PMID: 20519393
PDF is available here.
PDF is available here.
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Journal of Virology (84)1 2010
Abstract
We mapped a residue on APOBEC3H that determines this partial Vif sensitivity. However, it is unclear how HIV-1 can replicate in vivo without the ability to neutralize APOBEC3H antiviral activity. In order to directly address this question, we cloned vif genes from HIV-1-infected individuals with dif...
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PMID: 19828612
PDF is available here.
PDF is available here.
Biochemistry (Washington) (48)33 2009
Abstract
We have employed the biomimetic peptide HCCHp (HIV-1 Vif amino acids 101-142) in order to determine the zinc ligands and investigate the role of zinc binding in Cul5 recognition. Using CD spectroscopy, a competitive zinc binding assay, and a light scattering assay, we found that mutation of the cons...
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PMID: 19588889
PDF is available here.
PDF is available here.
Abstract
We show that PKA binds and specifically phosphorylates A3G at Thr32 in vitro and in vivo. This phosphorylation event reduces the binding of A3G to Vif and its subsequent ubiquitination and degradation, and thus promotes A3G antiviral activity. Computer-assisted structural modeling and mutagenesis st...
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PMID: 18836454
PDF is available here.
PDF is available here.
Abstract
We have determined the crystal structure of the HIV Vif BC box in complex with human ElonginB and ElonginC. This complex presents direct structural evidence of the recruitment of a human ubiquitin ligase by a viral BC box protein that mimics the conserved interactions of cellular ubiquitin ligases....
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PMID: 18562529
PDF is available here.
PDF is available here.
Journal of Virology (82)18 2008
Abstract
We show that in contrast to the expression of Vpr, the expression of Vif does not preclude cell division, and therefore, Vif causes delay and not arrest in G(2). We also demonstrate that the interaction of Vif with the ubiquitin ligase is required for cell cycle disruption, as was previously shown f...
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PMID: 18596088
PDF is available here.
PDF is available here.
Abstract
We demonstrate that both HIV-1 and SIVagm Vif can act in a proteasome-dependent manner to overcome A3C. SIVagm Vif requires the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase for the degradation of A3C as well as the suppression of its antiviral activity. Mutation of a residue critical for the specie...
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PMID: 18419775
PDF is available here.
PDF is available here.
Abstract
Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated wi...
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PMID: 18261756
PDF is available here.
PDF is available here.
Abstract
We show that naturally occurring HIV-1 Vif point mutants with suboptimal anti-APOBEC3G activity induce the appearance of proviruses with lamivudine (3TC) drug resistance-associated mutations before any drug exposure. These mutations, ensuing from cytidine deamination events, were detected in >40% of...
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PMID: 18391217
PDF is available here.
PDF is available here.
Abstract
Expression of HIV-1 vpr appears to enhance the protein levels of Vif both in fission yeast and mammalian cells. A similar enhancement effect of APOBEC3G by Vpr was also detected in mammalian cells. Interestingly, however, the increased Vif protein level by Vpr did not result in more APOBEC3G degrada...
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PMID: 18414697
PDF is available here.
PDF is available here.
Abstract
We reasoned that this failure was due to the lack of appropriate targeting. Thus, we fused A3A to another viral protein, Vpr, which binds p6 in Gag and is incorporated into viral cores. Indeed, the Vpr.A3A chimera but not A3A was found abundantly in the viral core. It also restricted potently the re...
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PMID: 18057006
PDF is available here.
PDF is available here.
Abstract
Our results clearly indicate that R88 delivers A3G into Vif(+) HIV-1 particles and inhibits infectivity and spread of the virions among CD4(+) T cells. This study provides evidence for an effective strategy to modify a host protein with innate anti-HIV-1 activity and rescue its potent anti-HIV poten...
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PMID: 18414671
PDF is available here.
PDF is available here.
Abstract
These results clearly indicate that CEM.NKR cells express a HIV inhibitory gene(s). Further characterization of this novel gene product(s) will reveal a new antiretroviral mechanism that directly inactivates wild type HIV-1....
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PMID: 18665212
PDF is available here.
PDF is available here.
Immunology (26) 2008
Abstract
We summarize current understanding of the mechanism of action of the APOBEC3 family of enzymes, their intriguing regulation within cells, the impact of these enzymes on viral evolution and disease progression, and their roles in controlling not only the replication of exogenous retroviruses but also...
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PMID: 18304004
PDF is available here.
PDF is available here.
Journal of Virology (81)24 2007
Abstract
We demonstrate that several rhesus macaque APOBEC3 (rhAPOBEC3) proteins are capable of inhibiting HIV-1 infectivity. There was considerable variation in the ability of a panel of Vif proteins to induce degradation of rhAPOBEC3 proteins, and mutations within HIV-1 Vif that render it capable of degrad...
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PMID: 17942564
PDF is available here.
PDF is available here.
Abstract
We used chemical cross-linking, proteolysis, and mass spectrometry. Cross-linking showed evidence of monomer, dimer, and trimer species via denaturing gel analysis and an additional tetramer via western blot analysis. We identified 47 unique linear peptides and 24 (13 intramolecular; 11 intermolecul...
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PMID: 17598142
PDF is available here.
PDF is available here.
Journal of General Virology (88)Pt 10 2007
Abstract
This report characterizes lentivirus attenuation associated with a vif mutation by inoculation of newborn kittens with a vif-deleted feline immunodeficiency virus provirus plasmid (FIV-pPPRDeltavif). Virus in peripheral blood, antiviral antibody or CD4 T-cell count alterations were not detected in k...
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PMID: 17872533
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (282)36 2007
Abstract
We performed the first characterization of Vif/nucleic acid interactions using Vif intrinsic fluorescence. We determined the affinity of Vif for RNA fragments corresponding to various regions of the HIV-1 genome. Our results demonstrated preferential and moderately cooperative binding for RNAs corre...
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PMID: 17609216
PDF is available here.
PDF is available here.
Abstract
Journal of Virology (81)15 2007
Abstract
We recently demonstrated that although APO3G has a natural tendency to form RNA-dependent homo-multimers, multimerization was not essential for encapsidation into HIV-1 virions or antiviral activity. We now demonstrate that a multimerization-defective APO3G variant (APO3G C97A) is able to assemble i...
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PMID: 17522211
PDF is available here.
PDF is available here.
Journal of Virology (81)15 2007
Abstract
We performed an extensive mutational analysis of HIV-1 Vif. Our analysis revealed two distinct Vif determinants, amino acids Y(40)RHHY(44) and D(14)RMR(17), which are essential for binding to A3G and A3F, respectively. Interestingly, mutation of the A3G-binding region increased Vif's ability to supp...
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PMID: 17522216
PDF is available here.
PDF is available here.
Journal of Virology (81)15 2007
Abstract
We now report a novel function of African green monkey simian immunodeficiency virus (SIVagm) Vif that promotes replication of SIVagm in human cells lacking detectable deaminase activity. We found that cyclophilin A (CypA) was excluded from wild-type SIV particles but was efficiently packaged into v...
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PMID: 17522232
PDF is available here.
PDF is available here.
Journal of Virology (81)13 2007
Abstract
We examined the metabolism of A3G-exposed viral DNA. We observed that an overall 35-fold decrease in viral infectivity was accompanied by a five- to sevenfold reduction in viral DNA synthesis. Wild-type A3G induced an additional fivefold decrease in the amount of viral DNA that was integrated into t...
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PMID: 17428871
PDF is available here.
PDF is available here.
FASEB Journal (21)8 2007
Abstract
We have now demonstrated that E4orf6-mediated p53 degradation requires Cul5. Furthermore, we have identified a lentiviral Vif-like BC-box motif in E4orf6 that is highly conserved among adenoviruses from multiple species. More importantly, we have shown that this Vif-like BC-box is essential for the...
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PMID: 17351129
PDF is available here.
PDF is available here.
Abstract
We have examined the requirements of vif for replication of a FIV strain isolated from a non-domestic felid, Otocolobus manul (FIV-Oma). In agreement with others, we find that replication of FIV vif mutant molecular clones in CrFK cells is highly attenuated. Initial attempts to rescue vif mutant vir...
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PMID: 17169394
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (282)16 2007
Abstract
We have demonstrated that the result of C to U conversion in minus-stranded DNA of human immunodeficiency virus type 1 (HIV-1) could trigger a degradation of nascent viral DNA mediated by uracil DNA glycosylases-2 (UNG2) and apurinic/apyrimidinic endonuclease (APE). Since antiviral activity of APOBE...
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PMID: 17272283
PDF is available here.
PDF is available here.
Abstract
We determined the quantities of A3G molecules that are incorporated in Deltavif virions. We combined three experimental approaches-reversed-phase high-pressure liquid chromatography (HPLC), scintillation proximity assay (SPA), and quantitative immunoblotting-to determine the molar ratio of A3G to HI...
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PMID: 17126871
PDF is available here.
PDF is available here.
Journal of Virology (81)8 2007
Abstract
We have employed molecular genetics to define features of A3G that are required for its interaction with Vif. Using alanine-scanning mutations and multiple different substitutions at key residues, we confirm the central role played by the aspartic acid at position 128 and identify proline 129 and as...
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PMID: 17267497
PDF is available here.
PDF is available here.
Abstract
We demonstrate that Vif also contributes to the arrest of HIV-1 infected cells in the G(2) phase of the cell cycle. Viruses deleted in Vif or Vpr induce less cell cycle arrest than wild-type virus, while cells infected with HIV-1 deleted in both Vif and Vpr have a cell cycle profile equivalent to th...
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PMID: 17056089
PDF is available here.
PDF is available here.
Abstract
We are to understand how APOBEC proteins protect host genomes from invading nucleic acids....
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PMID: 17303427
PDF is available here.
PDF is available here.
Abstract
We have developed a cell culture-based assay to measure Vif-induced hA3G degradation. The assay is based on alpha-complementation, the ability of beta-galactosidase fragments to complement in trans. hA3G expressed with a fused alpha-peptide was enzymatically active, complemented a coexpressed omega-...
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PMID: 17049578
PDF is available here.
PDF is available here.
Abstract
We demonstrate here that a peptide motif in the C terminus of the HTLV-1 nucleocapsid (NC) domain inhibits hA3G packaging into nascent virions. Mutation of amino acids within this region resulted in increased levels of hA3G incorporation into virions and increased susceptibility to hA3G restriction....
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PMID: 17299050
PDF is available here.
PDF is available here.
Abstract
VIF is one of the six accessory proteins of HIV-1. It has been shown to be necessary for the survival of HIV-1 in the human body and for the retention of viral infectivity. It is strongly expected that a new therapeutic strategy against HIV-1 infection could be realized by blocking the biological pa...
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PMID: 17285170
PDF is available here.
PDF is available here.
Abstract
These results indicate that antiviral drugs that target the conserved functional domains within Vif, Vpr or Vpu could be active against all circulating subtypes, including HIV-1 subtype C....
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PMID: 17331040
PDF is available here.
PDF is available here.
Journal of Microbiology (45)1 2007
Abstract
Nucleotide and amino acid substitution pattern in vif gene of the Korean clade of HIV-1 isolated from Koreans were analyzed using consensus sequences. At nucleotide level, transition/transversion substitution ratio was 1.88, and nonsynonymous/synonymous substitution ratio was 2.67, suggesting a dive...
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PMID: 17342060
PDF is available here.
PDF is available here.
Abstract
We demonstrate that the PcG-like genes in Caenorhabditis elegans, sop-2 and sor-3, regulate the formation of dopaminergic and serotonergic neurons and several other neuronal properties. sor-3 encodes a novel protein containing an MBT repeat, a domain that contains histone-binding activity and is pre...
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PMID: 17215367
PDF is available here.
PDF is available here.
Molecular Immunology (44)4 2007
Abstract
We show that Vif can counteract AID's activity in E. coli in absence of specific eukaryotic co-factors necessary for AID induced somatic hypermutation, gene conversion and to stimulate class switch recombination in B-cells. We show that AID inhibition is mediated by a direct protein-protein interact...
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PMID: 16580072
PDF is available here.
PDF is available here.
Nucleic Acids Research (35)15 2007
Abstract
We show that Vif is able to anneal primer tRNA(Lys3) to the viral RNA, to decrease pausing of reverse transcriptase during (-) strand strong-stop DNA synthesis, and to promote the first strand transfer. Vif also stimulates formation of loose HIV-1 genomic RNA dimers. These results indicate that Vif...
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PMID: 17660191
PDF is available here.
PDF is available here.
Abstract
Nature Medicine (13)1 2007
Abstract
We have designed new polyvalent vaccine antigens comprised of sets of 'mosaic' proteins, assembled from fragments of natural sequences via a computational optimization method. Mosaic proteins resemble natural proteins, and a mosaic set maximizes the coverage of potential T-cell epitopes (peptides of...
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PMID: 17187074
PDF is available here.
PDF is available here.
FASEB Journal (21)1 2007
Abstract
We demonstrated a requirement for zinc for Vif function in vivo. Treatment with TPEN at an IC50 of 1.79 microM inhibits Cul5 recruitment and APOBEC3G (A3G) degradation. Zinc chelation prevented Vif function in infectivity assays, allowing the virus to become sensitive to the antiviral activity of A3...
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PMID: 17135358
PDF is available here.
PDF is available here.
Abstract
We find that full-length HIV-1 Vif, as well as a HCCH peptide, is capable of binding to zinc with high specificity. Zinc binding induces a conformational change that leads to the formation of large protein aggregates. EDTA reversed aggregation and regenerated the apoprotein conformation. Cysteine mo...
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PMID: 17132731
PDF is available here.
PDF is available here.
Journal of Microbiology (44)6 2006
Abstract
We attempted to identify and characterize the Korean clade using all vif gene sequences isolated from Koreans registered in the NCBI GenBank database (n = 233). Most (77 %) of the Korean isolates belonged to the Korean clade as a large subcluster in subtype B, designated the Korean clade subtype B (...
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PMID: 17205044
PDF is available here.
PDF is available here.
Current Drug Targets (7)12 2006
Abstract
Vif is an HIV accessory protein whose primary function is to negate the action of APOBEC3G, a naturally occurring cellular inhibitor of HIV replication. Vif acts by binding to APOBEC3G, inducing its protein degradation within infected cells and reducing its levels in progeny virions. Interventions t...
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PMID: 17168833
PDF is available here.
PDF is available here.
Journal of Virology (80)23 2006
Abstract
We provide evidence here that a decrease in the synthesis of the DNA by reverse transcriptase may account for a significant part of this reduction. During the infection of cells with Vif-negative HIV-1 produced from 293T cells transiently expressing hA3G, much of the inhibition of early (> or =50% r...
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PMID: 16971427
PDF is available here.
PDF is available here.
Journal of Virology (80)21 2006
Abstract
We studied the antiretroviral activities of the human APOBEC3DE and APOBEC3H. We found that only APOBEC3DE had antiretroviral activity for HIV-1 or SIV and that Vif suppressed this antiviral activity. APOBEC3DE was encapsidated and capable of deaminating cytosines to uracils on viral minus-strand DN...
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PMID: 16920826
PDF is available here.
PDF is available here.
Abstract
A variety of mechanisms of innate immunity that protect organisms from retroviral infections, including HIV, are known. Lentiviruses express viral infectivity factor (Vif) protein that has the ability to counter antiviral activity exhibited by the recently discovered host cytidine deaminases APOBEC3...
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PMID: 17073615
PDF is available here.
PDF is available here.
Abstract
We previously demonstrated that the expression in cells of human immunodeficiency virus type 1 (HIV-1) Vif is maintained at low level by proteasome-degradation. We examined the contribution of 16 lysines present in Vif (NL432 clone), which is composed of 192 amino acids (aa), to its expression withi...
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PMID: 16964423
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (281)39 2006
Abstract
We purified a biologically active tandem affinity-tagged A3G from human HEK293T cells. Mass spectrometry and coimmunoprecipitation from HEK293T and T lymphocyte extracts identified many RNA-binding proteins specifically associated with A3G and A3F, including poly(A)-binding proteins (PABPs), YB-1, R...
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PMID: 16887808
PDF is available here.
PDF is available here.
Journal of Virology (80)18 2006
Abstract
We describe a population level analysis of HIV-1 hypermutation in [corrected] clade B proviral DNA sequences (n = 127). G-->A hypermutation conforming to expected APOBEC3G polynucleotide sequence preferences was inferred in 9.4% (n = 12) of the HIV-1 sequences, with a further 2.4% (n = 3) conforming...
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PMID: 16940537
PDF is available here.
PDF is available here.
Abstract
Abstract
Reverse transcription (RTn) in HIV-infected cells occurs in a nucleoprotein complex termed the reverse transcription complex (RTC). RTCs containing RT activity and integrase (IN) were shown to be heterogeneous in size and density on sucrose velocity and equilibrium gradients. WT and Vif-deficient (D...
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PMID: 16631224
PDF is available here.
PDF is available here.
Current Drug Targets (7)7 2006
Abstract
We suggest that the resulting crippled, defective HIV (dHIV) variants could interfere with replication of "wild type" viruses and curbe disese progression in long term non-progressor individuals. Vif, an accessory protein encoded by HIV, counteracts APOBEC3G/F action. We speculate that small molecul...
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PMID: 16842218
PDF is available here.
PDF is available here.
Journal of Biological Chemistry (281)25 2006
Abstract
We report that a region of Vif (residues 100-142) upstream of the BC-box binds selectively to Cul5 in the absence of EloC. This region contains a zinc coordination site HX5CX17-18CX3-5H (HCCH), with His/Cys residues at positions 108, 114, 133, and 139 coordinating one zinc ion. The HCCH zinc coordin...
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PMID: 16636053
PDF is available here.
PDF is available here.
Abstract
We report that HIV-1 Vif is a novel zinc-binding protein containing an H-x(5)-C-x(17-18)-C-x(3-5)-H motif that is distinct from other recognized classes of zinc fingers. Zinc-binding stabilized a conserved hydrophobic interface within the HCCH motif that is critical for Vif-Cul5 E3 assembly and Vif...
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PMID: 16530799
PDF is available here.
PDF is available here.
Journal of Virology (80)12 2006
Abstract
Human APOBEC3F (hA3F) and APOBEC3G (hA3G) are antiretroviral cytidine deaminases that can be encapsidated during virus assembly to catalyze C-->U deamination of the viral reverse transcripts in the next round of infection. Lentiviruses such as human immunodeficiency virus (HIV) and simian immunodefi...
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PMID: 16731937
PDF is available here.
PDF is available here.
Abstract
We compare the properties of APOBEC3F and APOBEC3G from human, macaque, and African green monkey (AGM). While all APOBEC proteins tested exhibited anti-HIV-1 activity, human APOBEC3F was, surprisingly, 10- to 50-fold less potent than human APOBEC3G. However, similar discrepancies in antiviral potenc...
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PMID: 16460778
PDF is available here.
PDF is available here.
Medical Science Monitor (12)5 2006
Abstract
The APOBEC (acronym for apolipoprotein B editing catalytic polypeptide) family of cytidine deaminases are widely distributed in the biological world and play a central role in diverse enzymatic pathways. Members of this family (APOBEC3G and APOBEC3F) have been recently shown to be able to restrict H...
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PMID: 16641889
PDF is available here.
PDF is available here.
PLoS Pathogens (2)5 2006
Abstract
We investigated the subcellular localization of the protein. Herein, we report that APOBEC3G localizes to mRNA processing (P) bodies, cytoplasmic compartments involved in the degradation and storage of nontranslating mRNAs. Biochemical analysis revealed that APOBEC3G localizes to a ribonucleoprotein...
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PMID: 16699599
PDF is available here.
PDF is available here.
Abstract
We review the research that led up to the identification of A3G and the mechanism that the human immunodeficiency virus protein Vif developed to evade A3G's antiviral activities....
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PMID: 16720549
PDF is available here.
PDF is available here.