Minor contribution of HLA class I-associated selective pressure to the variability of HIV-1 accessory protein Vpu

Hasan, Zahidah; Carlson, Jonathan M.; Gatanaga, Hiroyuki; Le, Anh Q.; Brumme, Chanson J.; Oka, Shinichi; Brumme, Zabrina L.; Ueno, Takamasa

doi:10.1016/j.bbrc.2012.04.002

Cited by 8 publications

(12 citation statements)

References 22 publications

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“…More than 95% of the individuals recruited in this study were of Japanese origin and men who have sex with men (MSM) were the predominant population in this cohort (Table I). In addition, the most frequently observed HLA-A, -B, and -C alleles in this cohort are HLA-A Ã 24:02, HLA-B Ã 52:01, and HLA-C Ã 01:02, respectively, consistent with HLA allele frequency of Japanese population reported previously [Itoh et al, 2005;Hasan et al, 2012;Chikata et al, 2014].…”

Section: Sequence Variability Of Hiv-1 Accessory Protein Vprsupporting

confidence: 91%

Identification of two unique naturally occurring Vpr sequence polymorphisms associated with clinical parameters in HIV‐1 chronic infection

Kamori

Hasan

Ohashi

et al. 2016

Journal of Medical Virology

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HIV-1 viral protein R (Vpr) plays important roles in HIV-1 replication. Despite the identification of a number of HLA class I-associated immune escape mutations; it is yet known whether immune-driven Vpr polymorphisms are associated with disease outcome. Hereby, we comprehensively analyzed Vpr sequence polymorphisms and their association with disease outcome and host HLA genotypes, by using plasma viral RNA isolated from 444 HLA-typed, treatment-naïve, chronically HIV-1 infected individuals. Vpr amino acid residues at positions 13, 37, 45, 55, 63, 77, 84, 85, 86, and 93 were significantly associated with patients' plasma viral load and/or CD4 count. Further analysis revealed Ala at position 55 was significantly associated with lower plasma viral load; and Thr at position 63 was significantly associated with lower plasma viral load and higher CD4 count. Also, the number of amino acid residues at the two positions, located in a functionally important α-helical domain, correlated inversely with plasma viral load and positively with CD4 count. Moreover, a phylogenetically corrected method revealed residues at positions 55 and 63 are associated with patients' HLA genotypes. Taken together, our results suggest that Vpr polymorphisms at functionally important and immune-reactive sites may contribute, at least in part, to viral replication and disease outcome in vivo. J. Med. Virol. 89:123-129, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Sequence Variability Of Hiv-1 Accessory Protein Vprsupporting

confidence: 91%

Identification of two unique naturally occurring Vpr sequence polymorphisms associated with clinical parameters in HIV‐1 chronic infection

Kamori

Hasan

Ohashi

et al. 2016

Journal of Medical Virology

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“…Conversely, the highly variable Vpu protein exhibited the least evidence of HLA-driven evolution (26.3% [P ϭ 0.009]) ( Fig. 1) (19,52,60). Across the entire HIV-1 proteome, polymorphisms at 804 of 1,481 (35.2%) variable sites were associated with at least one HLA allele.…”

Section: Resultsmentioning

confidence: 99%

“…The proportion of population-level sequence variation attributable, at least in part, to HLA (defined as the proportion of sites in a given protein harboring at least one HLA-associated polymorphism) differs markedly by protein and is independent of the protein's overall conservation. For example, whereas the majority of variable Nef codons are attributable, at least in part, to HLA class I-mediated pressures, this explains only a quarter of Vpu sequence variation, implying the existence of other host factors in driving evolution of this viral gene (40,52,112) (to provide context, nearly 40% of variable sites in the highly conserved p24…”

Section: Discussionmentioning

confidence: 99%

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

Carlson

Brumme

Martin

et al. 2012

J Virol

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i HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles. Over 2,100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally defined cytotoxic T-lymphocyte (CTL) epitope. Differential CTL escape patterns between closely related HLA alleles were common and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues represented the most frequently detected escape type: these occurred nearly 2-fold more frequently than expected by chance and were computationally predicted to reduce peptide-HLA binding nearly 10-fold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multisite and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV's structural and functional proteins. Thus, the factors defining protective cellular immune responses may be more complex than simply targeting conserved viral regions. The results provide new information to guide vaccine design and immunogenicity studies. HIV-1 is notorious for its genetic diversity and its ability to adapt to selection pressures (44,87,116). Despite this, within-host HIV-1 evolution in response to antiretroviral (61, 72), host cellular immune (15,50,71,94,95), antibody (46), and vaccine-induced (103) selection pressures occurs along generally predictable mutational pathways (3, 84). Studying these evolutionary pathways can offer insight into the immunopathogenesis of HIV-1 and may help inform the design of immune-based interventions and vaccines.Substantial progress has been made in our understanding of HIV-1's ability to evade human leukocyte antigen (HLA) class I-restricted CD8 ϩ cytotoxic T-lymphocytes (CTL). In particular, application of novel statistical methods (13,25,84) to large population-based data sets of linked host and viral genetic information has facilitated the systematic identification of HLA-associated immune escape and covarying mutations in 20,60,81,99,104), revealing important insights into HIV-1 adaptation to its host. We now appreciate that immune selection represents a major force shaping HIV-1 diversity (3,80,...

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“…In contrast, t/f viruses exhibited higher Vpu entropy (median 0.25; IQR: 0.00-0.65), confirming previous reports of substantial Vpu genetic variability. [37][38][39] As HIV-1C structural proteins generally exhibit lower entropy in early compared with chronic infection, 18 we hypothesized that accessory proteins of t/f viruses would also demonstrate reduced interpatient variability compared with HIV-1C chronically infected patients. As our cohort was only followed up to 500 days p/s, we used HIV-1C sequences from the LANL HIV database (Vif and Vpr n = 187; Vpu n = 197), the majority from Southern African countries (Supplementary Table S1), to represent accessory protein diversity in chronic infection, defined as >1,000 days postinfection/seroconversion.…”

Section: Clinical Characteristics and Interpatient Viral Quasispeciesmentioning

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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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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Minor contribution of HLA class I-associated selective pressure to the variability of HIV-1 accessory protein Vpu

Cited by 8 publications

References 22 publications

Identification of two unique naturally occurring Vpr sequence polymorphisms associated with clinical parameters in HIV‐1 chronic infection

Identification of two unique naturally occurring Vpr sequence polymorphisms associated with clinical parameters in HIV‐1 chronic infection

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

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

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