Effect of HIV-1 Vif variability on progression to pediatric AIDS and its association with APOBEC3G and CUL5 polymorphisms

Maio, Federico A. De; Rocco, Carlos; Aulicino, Paula; Bologna, Rosa; Mangano, Andrea; Sen, Luisa

doi:10.1016/j.meegid.2011.04.020

Cited by 22 publications

(18 citation statements)

References 30 publications

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“…7). A recent analysis of HIV-1 Vif sequence variation in an Argentinean pediatric cohort (7) showed that approximately 70% of subtype F strains encoded FH at positions 39/48, while 30% carried ZH or XN combinations (where Z indicates any amino acid other than F, and X denotes any residue), suggesting that the majority of subtype F strains likely counteract A3H hapII.…”

Section: Discussionmentioning

confidence: 99%

The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H

Binka

Ooms

Steward

et al. 2012

J Virol

107

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The APOBEC3 family comprises seven cytidine deaminases (APOBEC3A [A3A] to A3H), which are expressed to various degrees in HIV-1 susceptible cells. The HIV-1 Vif protein counteracts APOBEC3 restriction by mediating its degradation by the proteasome. We hypothesized that Vif proteins from various HIV-1 subtypes differ in their abilities to counteract different APOBEC3 proteins. Seventeen Vif alleles from seven HIV-1 subtypes were tested for their abilities to degrade and counteract A3G, A3F, and A3H haplotype II (hapII). We show that most Vif alleles neutralize A3G and A3F efficiently but display differences with respect to the inhibition of A3H hapII. The majority of non-subtype B Vif alleles tested presented some activity against A3H hapII, with two subtype F Vif variants being highly effective in counteracting A3H hapII. The residues required for activity were mapped to two residues in the amino-terminal region of Vif (positions 39F and 48H). Coimmunoprecipitations showed that these two amino acids were necessary for association of Vif with A3H hapII. These findings suggest that the A3H hapII binding site in Vif is distinct from the regions important for A3G and A3F recognition and that it requires specific amino acids at positions 39 and 48. The differential Vif activity spectra, especially against A3H hapII, suggest adaptation to APOBEC3 repertoires representative of different human ancestries. Phenotypic assessment of anti-APOBEC3 activity of Vif variants against several cytidine deaminases will help reveal the requirement for successful replication in vivo and ultimately point to interventions targeting the Vif-APOBEC3 interface.

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Section: Discussionmentioning

confidence: 99%

The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H

Binka

Ooms

Steward

et al. 2012

J Virol

107

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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

181

202

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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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“…Previous studies have addressed G-to-A hypermutation and APOBEC3G sequence variations on disease progression in infected children [36], [37]. Our study, however, describes for the first time the analysis of APOBEC3G and 3F mRNA expression levels in an infected pediatric setting.…”

Section: Discussionmentioning

confidence: 96%

Expression of APOBEC3G/3F and G-to-A Hypermutation Levels in HIV-1-Infected Children with Different Profiles of Disease Progression

et al. 2011

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Objective Increasing evidence has accumulated showing the role of APOBEC3G (A3G) and 3F (A3F) in the control of HIV-1 replication and disease progression in humans. However, very few studies have been conducted in HIV-infected children. Here, we analyzed the levels of A3G and A3F expression and induced G-to-A hypermutation in a group of children with distinct profiles of disease progression.Methodology/Principal Findings Perinatally HIV-infected children were classified as progressors or long-term non-progressors according to criteria based on HIV viral load and CD4 T-cell counts over time. A group of uninfected control children were also enrolled in the study. PBMC proviral DNA was assessed for G-to-A hypermutation, whereas A3G and A3F mRNA were isolated and quantified through TaqMan® real-time PCR. No correlation was observed between disease progression and A3G/A3F expression or hypermutation levels. Although all children analyzed showed higher expression levels of A3G compared to A3F (an average fold of 5 times), a surprisingly high A3F-related hypermutation rate was evidenced in the cohort, irrespective of the child's disease progression profile.Conclusion Our results contribute to the current controversy as to whether HIV disease progression is related to A3G/A3F enzymatic activity. To our knowledge, this is the first study analyzing A3G/F expression in HIV-infected children, and it may pave the way to a better understanding of the host factors governing HIV disease in the pediatric setting.

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Effect of HIV-1 Vif variability on progression to pediatric AIDS and its association with APOBEC3G and CUL5 polymorphisms

Cited by 22 publications

References 30 publications

The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H

The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H

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

Expression of APOBEC3G/3F and G-to-A Hypermutation Levels in HIV-1-Infected Children with Different Profiles of Disease Progression

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