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Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1.

ABSTRACT: Background:Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies. Methods:To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 transmission pairs from previous studies using mixed-effects linear regression and an approach to approximate the unobserved transmitted virus. Results:The recipient partner had a shorter V1-V4 region and fewer potential N-linked glycosylation sites (PNGS) than sequences from the source partner. We also detected a trend toward more PNGS and lower isoelectric points in transmitted sequences with source partner and the evolutionary tendency to shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points in the recipient following transmission. Conclusions:By using all available well-characterized env sequences from transmission pairs via sexual exposure, we were able to identify several important virologic factors that may be important in the development of biomedical preventive interventions.

SUBMITTER: Choi JY

PROVIDER: S-EPMC6281333 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1.

Choi Jun Yong JY Pond Sergei L Kosakovsky SLK Anderson Christy M CM Richman Douglas D DD Smith Davey M DM

The Journal of infectious diseases 20170501 10

<h4>Background</h4>Investigations into which human immunodeficiency virus type 1 (HIV-1) sequence features may be selected for transmission during sexual exposure have been hampered by the small number of characterized transmission pairs in individual studies.<h4>Methods</h4>To boost statistical power to detect differences in glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we reanalyzed all available 2485 env sequences derived from 114 subjects representing 58 tran ...[more]

PMID: 28419276

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Project description:BackgroundThe HIV envelope (Env) promotes viral entry in the host cell. During this process, Env undergoes several conformational changes to ensure its function. At the same time, the gp120 component of Env is the protein of the virus presenting the largest genetic diversity. Understanding how the virus maintains the balance between the competing requirements for maintenance of functionality and antigenic variation of this protein is central for the comprehension of its strategies of evolution and can highlight vulnerable aspects of its replication cycle. We focused on the variable domains V1 and V2 of the HIV-1 gp120 that are involved in conformational changes and are critical for viral escape from antibody neutralization.ResultsDespite the extensive sequence diversity found in the epidemic for these regions and their location on the external face of the protein, we observed that replacing V1V2 of one primary isolate with that of another severely interferes with Env functionality in more than half of the cases studied. Similar results were obtained for intra- and intersubtype chimeras. These observations are indicative of an interference of genetic diversity in these regions with Env functionality. Therefore, despite the extensive sequence diversity that characterizes these regions in the epidemic, our results show that functional constraints seem to limit their genetic variation. Defects in the V1V2 chimeras were not relieved by the insertion of the V3 region from the same isolate, suggesting that the decrease in functionality is not due to perturbation of potential coevolution networks between V1V2 and V3. Within the V1V2 domain, the sequence of the hypervariable loop of the V1 domain seems to be crucial for the functionality of the protein.ConclusionsBesides the well-documented role of V1V2 in the interplay with the immune response, this work shows that V1 is also involved in the selection of functional envelopes. By documenting a compromise between the opposing forces of sequence diversification and retention of functionality, these observations improve our understanding of the evolutionary trajectories of the HIV-1 envelope gene.

Dataset Information

Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1.

Publications

Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human Immunodeficiency Virus Type 1.

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