. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "HIV-1 Vif, CBF-beta, CUL5, and ELOB/C form a complex that is required for Vif-mediated downregulation of A3G and A3F. CBF-beta regulates HIV-1 infectivity only in the presence of A3G" . "CUL5/RBX2/ELOB/ELOC/Vif/CBF-beta complex catalyzes polyubiquitin chain formation on A3G in the presence of ubiquitin E2 UBE2R1 (CDC34) or UBCH5b (UBE2D2)" . "A mutagenesis screen of CBF-beta surface residues reveals that a single amino acid change, F68D, disrupts HIV-1 Vif binding and its ability to degrade APOBEC3G" . "NF-IL6 facilitates the reverse transcription of HIV-1 by binding to and inhibiting the antiviral cytidine deaminase APOBEC3G. A mutation in NF-IL6 at Ser-288 weakens its binding to APOBEC3G and strongly inhibits HIV-1 replication" . "IFN-alpha enhances APOBEC3G expression and inhibits suppression of APOBEC3G by HIV-1 Vif" . "MDM2 reduces cellular Vif levels and reversely increases A3G levels, because the interaction between MDM2 and Vif prevents A3G from binding to Vif" . "Protein kinase A (PKA) binds and 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" . "Mutations in HIV-1 Vif PPLP motif (amino acids 161-164) reduces Vif binding to A3G without affecting its interaction with ElonginC and Cullin5" . "A potent small molecular compound VEC-5 protects APOBEC3G, APOBEC3F, and APOBEC3C from HIV-1 Vif-induced degradation and enhances A3G incorporation into HIV-1 virions by inhibiting the interaction between Vif and elongin C" . "Treatment with the membrane-permeable zinc chelator TPEN prevents Vif function, and causes the blockage of Cul5 recruitment and APOBEC3G (A3G) degradation" . "Small molecule RN-18 specifically inhibits HIV-1 Vif-mediated downregulation of APOBEC3C/F/G proteins by decreasing Vif protein levels when Vif interacts with these proteins" . "HIV-1 Vif K22E and RH41/42AA mutants are able to suppress the anti-viral activity of A3C, but are ineffective in suppressing the anti-viral activity of A3G. K22, R41, and H42 residues are important for Vif-mediated degradation of A3G, but not A3C" . "APOBEC3G in exosomes reduces accumulation of HIV-1 reverse transcription products and steady-state levels of HIV-1 Gag and Vif proteins" . "APOBEC3G, also known as CEM15, is a cellular inhibitor of HIV-1 replication which is suppressed by the viral Vif protein" . "HIV-1 Vif suppresses the inhibitory effects of APOBEC3G on HIV-1 replication by reducing its intracellular expression and inhibiting its virion encapsidation" . "HIV-1 Vif binds to amino acids 54-124 of APOBEC3G and causes its degradation through a proteasome dependent pathway" . "The ability of HIV-1 Vif to suppress the antiviral activity of APOBEC3G is dependent on the function of a Vif-Cul5-SCF complex involving Cul5, elongins B and C, and Rbx1" . "Co-immunoprecipitation assays show that HIV-1 Vif directly binds APOBEC3G to form a complex in vivo that accelerates the degradation of APOBEC3G via the ubiquitin-proteasome pathway" . "Mutation of amino acid S144 in HIV-1 HXB2 Vif significantly reduces the ability of Vif to inhibit the antiviral activity of APOBEC3G" . "A single amino acid replacement of Asp-128 in human APOBEC3G with the Lys-128 of African green monkey (AGM) APOBEC3G causes the enzyme to switch its interaction, becoming sensitive to SIV(AGM) Vif and resistant to HIV-1 Vif" . "The C-terminal domain (amino acid residues 156-193) of APOBEC3G is required for binding with HIV-1 Vif" . "Binding of APOBEC3G with HIV-1 Vif influences the localization of Vif, and mutation of the isoleucine at Vif amino acid 9 disrupts this interaction" . "The binding of HIV-1 Vif to APOBEC3G is specifically mediated by a strong interacting domain encompassing amino acids 85-99 in APOBEC3G and 169-192 in Vif" . "Highly conserved tryptophan residues in the N-terminal region of HIV-1 Vif are required for the suppression of both APOBEC3G and APOBEC3F" . "HIV-1 Vif, which suppresses both APOBEC3G and APOBEC3F antiviral function by inducing their degradation, may selectively remove these proteins from, and/or restrict their localization to, P-bodies" . "Mutations in the HIV-1 Vif HCCH motif (residues 108-139), BC box (residues 144-146), and Cul5-box (residues 163-169) result in the reduction of Vif-induced APOBEC3G degradation" . "Approximately 7 (+/-4) molecules of APOBEC3G are incorporated into HIV-1 Vif-negative virions produced from human PBMCs; HIV-1 Vif inhibits this incorporation" . "The overall negative charge of the 3-amino-acid motif Asp128, Pro129, and Asp130 in APOBEC3G appears critical for recognition by Vif. The immediately adjacent 4 amino acids, residues 124 to 127, are important for the packaging of A3G into HIV-1 particles" . "APOBEC3G C97A mutant binds to HIV-1 Vif but is resistant to degradation by Vif. Vif inhibits encapsidation of APOBEC3G C97A and restores viral infectivity" . "An extensive mutational analysis of HIV-1 Vif reveals that two distinct regions of Vif, amino acids Y(40)RHHY(44) and D(14)RMR(17), are essential for binding to A3G and A3F, respectively" . "HIV-1 Vif reduces cellular expression and packaging of A3G-3A chimera" . "In vitro biochemical and cell-based binding assays show residues 40 to 71 in the N terminus of Vif contain a nonlinear binding site for APOBEC3G. Mutation of the highly conserved residues His42/43 in this region inhibits Vif-APOBEC3G binding" . "Expression of hA3G fragments 1-156 or 157-384 dominantly inhibits the Vif-mediated degradation of full-length hA3G; only the N-terminal fragment inhibits the Vif/hA3G interaction" . "HIV-1 Vif induces the gradual transition of APO3G translated in vitro or expressed in HeLa cells from a low molecular mass (LMM) conformation to puromycin-sensitive high molecular mass (HMM) complexes" . "Suppression of viral infectivity by a peptide antagonist of Vif dimerization domain is dependent on the expression of Vif and hA3G" . "A3G without ubiquitylation is still degraded by proteasomes in an HIV-1 Vif-dependent manner. Polyubiquitynated Vif is critical for A3G proteasomal degradation" . "APOBEC3G fused with a virion-targeting polypeptide (amino acids 14-88) derived from HIV-1 Vpr is incorporated into Vif(+) HIV-1 particles and inhibits infectivity and spread of the virions among CD4(+) T cells" . "N-terminal region (amino acids 21-43) of HIV-1 Vif is important for suppression of APOBEC3G" . "Vif-deficient HIV-1 replicates as equally well as wild-type virus in CEM-T4 cells expressing high levels of A3G and A3F, indicating CEM-T4 cells lack a cellular co-factor for these endogenous antiretroviral proteins" . "A VxIPLx(4-5)LxPhix(2)YWxL motif (amino acids 55-72) in HIV-1 Vif is required for efficient interaction between Vif and A3G, Vif-mediated A3G degradation and virion exclusion" . "APOBEC3G fused with ubiquitin-associated domain 2 (UBA2) in HHR23A protein is more resistant to Vif-mediated protein degradation than APOBEC3G" . "Newly synthesized APOBEC3G is more sensitive to HIV-1 Vif-induced degradation than preexisting APOBEC3G" . "Amino acids 121 to 149 of A3G are essential for binding to the 40YRHHY44 region of HIV-1 Vif but not sufficient for A3G degradation" . "C-terminal half of HIV-1 Vif from subtype C virus possesses major determinant for A3G degradation" . "A novel conserved 69YXXL72 motif in HIV-1 Vif mediates binding to human A3G and its subsequent degradation. Tyr69 and Trp70 residues in the YXXL motif are required for binding to A3G in vitro" . "Human T cell line CEM.NKR clones display inhibition of HIV-1 replication although these clones retain low levels of A3DE, A3F, A3G, and A3H expression, suggesting that a novel restriction factor distinct from APOBEC3s exists in CEM.NKR cells" . "5' splice site D2 and an exonic splicing enhancer exist in the HIV-1 genome is to regulate the levels of vif mRNA and Vif protein in infected cells to counteract cellular restriction factor APOBEC3G" . "Residues K22, K26, Y30, and Y40 in the SLV/Ix4Yx9Y motif of HIV-1 Vif are important for the Vif-induced degradation and suppression of cellular APOBEC3G. The positively charged K26 is the most critical residue for A3G inactivation" . "The SLV portion of the Vif SLV/Ix4Yx9Y motif is required for Vif specificity for APOBEC3G degradation" . "Arginine substitutions for Lys-297, 301, 303, and 334 cause A3G resistant to Vif-mediated degradation. The mutant displays normal Vif binding and inhibits HIV-1 infection" . "Incorporation of HIV-1 Vif into virions is dependent on its interaction with A3G/A3F" . "Significant levels of ubiquitinated A3G and A3G20K/R are detected in the presence of HIV-1 Vif. Vif-induced ubiquitination of A3G and A3G20K/R is inhibited by Cul5deltaNedd8" . "HIV-1 Vif W21A, S32A, W38A, Y40A, Y69A, H108A, C114S, C133S, and H139A mutants have no viral ability to neutralize APOBEC3G" . "HIV-1 Vif mutants carrying mutations or deletions in the conserved HCCH (residues 108-139), SLQ (residues 144-149), and PPLP (residues 161-164) motifs have the ability to dominantly interfere with the wild-type Vif function to inhibit A3G" . "Residues G84, and, to a lesser extent, I87 and W89 within the (81)LGxGxxIxW(89) domain affect Vif binding to A3G and play very critical roles in A3G neutralizing activity" . "Compounds IMB-26 and IMB-35 bind directly to the hA3G protein, suppress HIV-1 Vif/hA3G interaction, and therefore protect hA3G from Vif-mediated degradation" . "The T(Q/D/E)x(5)ADx(2)(I/L) motif, located at residues 96 to 107 in HIV-1 Vif, plays a critical role in neutralizing activity toward A3G. This motif regulates Vif interaction with Cul5" . "Alternative splice removal of exon 2 or exons 3-5 of A3G produces proteins that do not interact with HIV-1 Vif and lack antiviral activity" . "APOBEC3G can escape the inhibition from Vif and retain its antiviral activity when it is expressed high enough" . "HIV-1 Vif inhibits the antiviral function of A3G in a subtype-dependent manner. The N-terminal region (amino acids 1-31) of subtype C-derived Vif protein is crucial for the anti-A3G activity" . "Introduction of two Vif-binding mutants (D128K and P129A) into the R88-A3G fusion protein shows that both R88-A3GD128K and R88-A3GP129A possess very potent anti-HIV activity" . "HSP70 interacts with both APOBEC3G and HIV-1 Vif, which stabilizes APOBEC3G and blocks Vif-mediated degradation of APOBEC3G" . "The N-terminal HA tag stabilizes A3G20K/R degradation induced by HIV-1 Vif, at least in part, by blocking Vif-mediated A3G polyubiquitination" . "HIV-1 Vif-22H mutant uses APOBEC3G hypermutation to develop resistance in certain non-B variants" . "Human A3G is a host restriction factor against hepatitis C virus (HCV). Exogenous HIV-1 Vif decreases intracellular hA3G and therefore enhances HCV proliferation" . "Three A3G mutants, containing duplicate CD1 domain (residues 65-100), duplicate CD2 domain (residues 257-291), or position switched CD domains, has no significant effect in A3G/Vif interaction and in incorporation into virions" . "Virion-encapsidated HIV-1 Vif, purified Vif protein and the Vif-derived peptide Vif25-39 inhibit the deamination activity of A3G" . "A3G upregulates NKG2D ligands through an ATM pathway. HIV-1 Vif counteracts this upregulation by decreasing A3G expression" . "HIV-1 Vif alleles from seven HIV-1 subtypes show their abilities to degrade and counteract A3G efficiently" . "CBF-beta isoform 1 and isoform 2 stabilize HIV-1 Vif to degrade A3G and increase viral infectivity" . "Residues N20, R24, L27, R30, Y59, K63, W94, R102, R122, W127, D128, D130, R136, F157, W175, and 22970171E191 in the APOBEC3G N-terminal cytidine deaminase domain are involved in the interaction with HIV-1 Vif" . "Residues Y222, Q237, R238, R239, W269, and K270 in the C-terminal cytidine deaminase domain are involved in the interaction with HIV-1 Vif" . "Affinity Capture-Western; Biochemical Activity; PCA; Reconstituted Complex" . "BioGRID" . "inhibits" . "downregulates" . "interacts with" . "inhibited by" . "disrupts" . "binds" . "degrades" . "induces ubiquitination of" .