Molecular Analysis of HIV Type 1 <i>vif</i> Sequences from Cape Town, South Africa

Jacobs, Graeme Brendon; Nistal, M; Laten, Annette; Rensburg, Estrelita Janse van; Rethwilm, Axel; Preiser, Wolfgang; Bodem, Jochen; Engelbrecht, Susan

doi:10.1089/aid.2008.0077

Cited by 12 publications

(9 citation statements)

References 15 publications

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“…The Vif oligomerization site 161-PPLP-164 was conserved throughout, confirming its central role in Vif function and viral infectivity during all stages of infection. At the phosphorylation site position 170, our findings are similar to previously published HIV-1 subtype C studies 36,52 where Val is the major amino acid in the transmitted viruses, although Ile is present in one patient.…”

Section: Figsupporting

confidence: 91%

“…The 90-RLRR-93 motif was not conserved in the transmitted viruses similar to previously reported subtype C analyses. 36,52 The residues, Ser 95 and Thr 96 , which are CKII and p44/42 mitogen-activated protein kinase phosphorylation sites, respectively, were relatively conserved in the transmitted viruses with variation present in one patient. As expected, the important His 108 , Cys 114 , Cys 133 , and His 139 (HCCH) zincbinding motif was completely conserved in the transmitted viruses from all 17 patients, as identified in previous subtype B and C analyses, 36,53,54 suggesting an important role for the HCCH-stabilized Vif-Cullin 5 interaction early in infection.…”

Section: Discussionmentioning

confidence: 99%

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Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

Rossenkhan

MacLeod

Brumme

et al. 2016

AIDS Research and Human Retroviruses

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Viral variants that predominate during early infection may exhibit constrained diversity compared with those found during chronic infection and could contain amino acid signature patterns that may enhance transmission, establish productive infection, and influence early events that modulate the infection course. We compared amino acid distributions in 17 patients recently infected with HIV-1C with patients with chronic infection. We found significantly lower entropy in inferred transmitted/founder (t/f) compared with chronic viruses and identified signature patterns in Vif and Vpr from inferred t/f viruses. We investigated sequence evolution longitudinally up to 500 days postseroconversion and compared the impact of selected substitutions on predicted human leukocyte antigen (HLA) binding affinities of published and predicted cytotoxic T-lymphocyte epitopes. Polymorphisms in Vif and Vpr during early infection occurred more frequently at epitope-HLA anchor residues and significantly decreased predicted epitope-HLA binding. Transmission-associated sequence signatures may have implications for novel strategies to prevent HIV-1 transmission.

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Section: Figsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

Rossenkhan

MacLeod

Brumme

et al. 2016

AIDS Research and Human Retroviruses

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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

187

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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“…Despite the availability of HIV-1 subtype C vif sequences [37–39], functional data regarding their anti-A3G activity remains very limited [31, 32]. We therefore cloned, sequenced and analysed HIV-1 subtype C vif alleles from patients homozygous for WT A3G, homozygous for A3G-H186R and from heterozygous patients [19].…”

Section: Resultsmentioning

confidence: 99%

Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes

Reddy

Ooms²,

Letko³

et al. 2016

Aids

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Objective The human cytidine deaminase APOBEC3G (A3G) potently restricts HIV-1 but the virus, in turn, expresses a Vif protein which degrades A3G. A natural A3G-H186R variant, common in African populations, has been associated with a more rapid AIDS disease progression, but the underlying mechanism remains unknown. We hypothesized that differences in HIV-1 Vif activity towards A3G wild-type (WT) and A3G-H186R contribute to the distinct clinical AIDS manifestation. Methods Vif variants were cloned from plasma samples of 26 South African HIV-1 subtype C infected patients that either express WT A3G or A3G-H186R. The Vif alleles were assessed for their ability to counteract A3G variants using Western blot and single-cycle infectivity assays. Results We obtained a total of 392 Vif sequences which displayed an amino acid sequence difference of 6.2–19.2% between patients. The intra-patient Vif diversity from patient groups A3GWT/WT, A3GWT/H186R and A3GH186R/H186R was similar. Vif variants obtained from patients expressing A3GWT/WT and A3GH186R/H186R were capable of counteracting both A3G variants with similar efficiency. However, the antiviral activity of A3G-H186R was significantly reduced in both the presence and absence of Vif, indicating that the A3G-H186R variant intrinsically exerts less antiviral activity. Conclusion A3G WT and A3G-H186R are equally susceptible to counteraction by Vif, regardless of whether the Vif variant was obtained from A3GWT/WT and A3GH186R/H186R patients. However, the A3G-H186R variant intrinsically displayed lower antiviral activity, which could explain the higher plasma viral loads and accelerated disease progression reported for patients expressing A3GH186R/H186R.

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Molecular Analysis of HIV Type 1 vif Sequences from Cape Town, South Africa

Cited by 12 publications

References 15 publications

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

Transmitted/Founder HIV-1 Subtype C Viruses Show Distinctive Signature Patterns in Vif, Vpr, and Vpu That Are Under Subsequent Immune Pressure During Early Infection

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

Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes

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