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Evaluation of global HIV/SIV envelope gp120 RNA structure and evolution within and among infected hosts.

ABSTRACT: Lentiviral RNA genomes contain structural elements that play critical roles in viral replication. Although structural features of 5'-untranslated regions have been well characterized, attempts to identify important structures in other genomic regions by Selective 2'-Hydroxyl Acylation analyzed by Primer Extension (SHAPE) have led to conflicting structural and mechanistic conclusions. Previous approaches accounted neither for sequence heterogeneity that is ubiquitous in viral populations, nor for selective constraints operating at the protein level. We developed an approach that augments SHAPE with phylogenetic analyses and applied it to investigate structure in coding regions (cRNA) within the HIV and SIV envelope genes. Analysis of single-genome SHAPE data with phylogenetic information from diverse lentiviral sequences argues against the conservation of a putative global gp120 RNA structure but points to the existence of core RNA sub-structures. Our findings establish a framework for considering sequence heterogeneity and protein function in de novo RNA structure inference approaches.

SUBMITTER: Rife Magalis B

PROVIDER: S-EPMC6014367 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Evaluation of global HIV/SIV envelope gp120 RNA structure and evolution within and among infected hosts.

Rife Magalis Brittany B Kosakovsky Pond Sergei L SL Summers Michael F MF Salemi Marco M

Virus evolution 20180101 1

Lentiviral RNA genomes contain structural elements that play critical roles in viral replication. Although structural features of 5'-untranslated regions have been well characterized, attempts to identify important structures in other genomic regions by Selective 2'-Hydroxyl Acylation analyzed by Primer Extension (SHAPE) have led to conflicting structural and mechanistic conclusions. Previous approaches accounted neither for sequence heterogeneity that is ubiquitous in viral populations, nor for ...[more]

PMID: 29951250

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Project description:BACKGROUND:The initial envelope (Env)-specific antibody response in acutely HIV-1-infected individuals and simian immunodeficiency virus (SIV)-infected rhesus monkeys (RMs) is dominated by non-neutralizing antibodies targeting Env gp41. In contrast, natural primate SIV hosts, such as African green monkeys (AGMs), develop a predominant Env gp120-specific antibody response to SIV infection. However, the fine-epitope specificity and function of SIV Env-specific plasma IgG, and their potential role on autologous virus co-evolution in SIV-infected AGMs and RMs remain unclear. RESULTS:Unlike the dominant linear gp41-specific IgG responses in RMs, SIV-infected AGMs demonstrated a unique linear variable loop 2 (V2)-specific plasma IgG response that arose concurrently with high gp120-directed antibody-dependent cellular cytotoxicity (ADCC) activity, and SIVsab-infected cell binding responses during acute infection. Moreover, SIV variants isolated from SIV-infected AGMs exhibited high amino acid mutation frequencies within the Env V1V2 loop compared to those of RMs. Notably, the linear V2-specific IgG epitope in AGMs overlaps with an analogous region of the HIV V2 loop containing the K169 mutation epitope identified in breakthrough viruses from RV144 vaccinees. CONCLUSION:Vaccine-elicited Env V2-specific IgG responses have been proposed as an immune correlate of reduced risk in HIV-1/SIV acquisition in humans and RMs. Yet the pathways to elicit these potentially-protective V2-specific IgG responses remain unclear. In this study, we demonstrate that SIV-infected AGMs, which are the natural hosts of SIV, exhibited high plasma linear V2-specific IgG binding responses that arose concurrently with SIV Env gp120-directed ADCC-mediating, and SIV-infected cell plasma IgG binding responses during acute SIV infection, which were not present in acutely SIV-infected RMs. The linear V2-specific antibody response in AGMs targets an overlapping epitope of the proposed site of vaccine-induced immune pressure defined in the moderately protective RV144 HIV-1 vaccine trial. Identifying host factors that control the early elicitation of Env V2-specific IgG and ADCC antibody responses in these natural SIV hosts could inform vaccination strategies aimed at rapidly inducing potentially-protective HIV-1 Env-specific responses in humans.

Dataset Information

Evaluation of global HIV/SIV envelope gp120 RNA structure and evolution within and among infected hosts.

Publications

Evaluation of global HIV/SIV envelope gp120 RNA structure and evolution within and among infected hosts.

Similar Datasets

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