A Naturally Occurring Vif Mutant (I107T) Attenuates Anti-APOBEC3G Activity and HIV-1 Replication

Peng, Jinyu; Ao, Zhujun; Matthews, Chris; Wang, Xiaoxia; Ramdahin, Sue; Chen, Xi; Li, Junhua; Chen, Liyu; He, Jianmei; Ball, Blake; Fowke, Keith R.; Plummer, Frank; Embreé, Joanne; Yao, Xiaojian

doi:10.1016/j.jmb.2013.05.015

Cited by 9 publications

(11 citation statements)

References 48 publications

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“…Mutations in the HIV-1 genome may affect its viral replication [10][11][12][13]. Four different HIV-1 genomic regions (pol, vif, env, and nef genes) were analyzed to detect potential signatures related to the selective pressure of GBV-C.…”

Section: Discussionmentioning

confidence: 99%

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HIV-1 and GBV-C co-infection in Venezuela

Rodríguez

Garzaro

Loureiro

et al. 2014

J Infect Dev Ctries

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Introduction: Co-infection with GB virus C (GBV-C) in patients infected with human immunodeficiency virus 1 (HIV-1) has been associated with prolonged survival. The aim of this study was to evaluate the prevalence of GBV-C infection among HIV-1-infected patients in Venezuela, and to determine the effects of the co-infection on the levels of relevant cytokines. Methodology: Plasma samples were collected from 270 HIV-1-seronegative and 255 HIV-1-seropositive individuals. GBV-C infection was determined by RT-PCR of the NS5 region and genotyped by sequence analysis of the 5´UTR region. HIV-1 strains were characterized by sequence analysis of pol, vif, env, and nef genes. Selected cytokines were evaluated by ELISA. Results: Ninety-seven of 525 (18.5%) plasma samples tested positive for GBV-C RNA. A significantly higher prevalence of GBV-C was found among HIV-1 patients compared to HIV-1-seronegative individuals (67/255, 26% versus 30/270, 11%; p < 0.001). Statistical difference was observed in the viral load between HIV-1+GBV-C+ and HIV-1+GBV-C-(p = 0.014), although no differences in CD4 + cell counts were found between both groups. TNFα concentration was higher in HIV-1

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Section: Discussionmentioning

confidence: 99%

“…Nevertheless, some of these factors have been shown to reduce susceptibility to HIV-1 infection [9]. HIV-1 genetic factors, as drug resistance mutation or mutation in the env or vif genes, may affect viral replication [10][11][12][13], and thus viral load; a selective pressure of GBV-C on HIV-1 genes may be not discarded.…”

Section: Introductionmentioning

confidence: 99%

HIV-1 and GBV-C co-infection in Venezuela

Rodríguez

Garzaro

Loureiro

et al. 2014

J Infect Dev Ctries

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“…Not surprisingly, the vif gene has high genetic variability 89; 256; 257; 258; 259 and subtype dependent amino acid substitutions 188; 260; 261 in patient samples with varying degrees of activity against A3 proteins. Interestingly, defective Vif alleles such as K22H that cannot efficiently neutralize A3G and A3F are readily detected in HIV-1 infected patients.…”

Section: A3 Restriction In Hiv-1 Infected Patientsmentioning

confidence: 99%

Multiple APOBEC3 Restriction Factors for HIV-1 and One Vif to Rule Them All

Desimmie

Delviks-Frankenberrry

Burdick

et al. 2014

Journal of Molecular Biology

184

214

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Several members of the APOBEC3 family of cellular restriction factors provide intrinsic immunity to the host against viral infection. Specifically, APOBEC3DE, APOBEC3F, APOBEC3G, and APOBEC3H haplotypes II, V, and VII provide protection against HIV-1Δvif through hypermutation of the viral genome, inhibition of reverse transcription, and inhibition of viral DNA integration into the host genome. HIV-1 counteracts APOBEC3 proteins by encoding the viral protein Vif, which contains distinct domains that specifically interact with these APOBEC3 proteins to ensure their proteasomal degradation, allowing virus replication to proceed. Here, we review our current understanding of APOBEC3 structure, editing and non-editing mechanisms of APOBEC3-mediated restriction, Vif-APOBEC3 interactions that trigger APOBEC3 degradation, and the contribution of APOBEC3 proteins to restriction and control of HIV-1 replication in infected patients.

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“…However, there have been debates on this issue (35)(36)(37)(38). Moreover, natural variations in Vif and A3G have been reported to affect their functions (39)(40)(41)(42). It remains unclear whether there are natural variations that alter vif mRNA levels in the HIV-1 genome.…”

Section: Hiv Vif (Virion Infectivity Factor) Is Essential For Viral Rmentioning

confidence: 99%

Natural Single-Nucleotide Variations in the HIV-1 Genomic SA1prox Region Can Alter Viral Replication Ability by Regulating Vif Expression Levels

Nomaguchi

Doi

Sakai

et al. 2016

J Virol

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We previously found that natural single-nucleotide variations located within a proximal region of splicing acceptor 1 (SA1prox) in the HIV-1 genome could alter the viral replication potential and mRNA expression pattern, especially the vif mRNA level. Here, we studied the virological and molecular basis of nucleotide sequence variations in SA1prox for alterations of viral replication ability. Consistent with our previous findings, variant clones indeed expressed Vif at different levels and grew distinctively in cells with various APOBEC3G expression levels. Similar effects were observed for natural variations found in HIV-2 SA1prox, suggesting the importance of the SA1prox sequence. To define nucleotides critical for the regulation of HIV-1 Vif expression, effects of natural SA1prox variations newly found in the HIV Sequence Compendium database on vif mRNA/Vif protein levels were examined. Seven out of nine variations were found to produce Vif at lower, higher, or more excessive levels than wild-type NL4-3. Combination experiments of variations giving distinct Vif levels suggested that the variations mutually affected vif transcript production. While low and high producers of Vif grew in an APOBEC3G-dependent manner, excessive expressers always showed an impeded growth phenotype due to defects in single-cycle infectivity and/or virion production levels. The phenotype of excessive expressers was not due primarily to inadequate expression of Tat or Rev, although SA1prox variations altered the overall HIV-1 mRNA expression pattern. Collectively, our results demonstrate that HIV SA1prox regulates Vif expression levels and suggest a relationship between SA1prox and viral adaptation/evolution given that variations occurred naturally. IMPORTANCEWhile human cells possess restriction factors to inhibit HIV-1 replication, HIV-1 encodes antagonists to overcome these barriers. Conflicts between host restriction factors and viral counterparts are critical driving forces behind mutual evolution. The interplay of cellular APOBEC3G and viral Vif proteins is a typical example. Here, we demonstrate that naturally occurring single-nucleotide variations in the proximal region of splicing acceptor 1 (SA1prox) of the HIV-1 genome frequently alter Vif expression levels, thereby modulating viral replication potential in cells with various ABOBEC3G levels. The results of the present study reveal a previously unidentified and important way for HIV-1 to compete with APOBEC3G restriction by regulating its Vif expression levels. We propose that SA1prox plays a regulatory role in Vif counteraction against APOBEC3G in order to contribute to HIV-1 replication and evolution, and this may be applicable to other primate lentiviruses.

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A Naturally Occurring Vif Mutant (I107T) Attenuates Anti-APOBEC3G Activity and HIV-1 Replication

Cited by 9 publications

References 48 publications

HIV-1 and GBV-C co-infection in Venezuela

HIV-1 and GBV-C co-infection in Venezuela

Multiple APOBEC3 Restriction Factors for HIV-1 and One Vif to Rule Them All

Natural Single-Nucleotide Variations in the HIV-1 Genomic SA1prox Region Can Alter Viral Replication Ability by Regulating Vif Expression Levels

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