Dataset Information

Rev-Rev Response Element Activity Selection Bias at the Human Immunodeficiency Virus Transmission Bottleneck.

ABSTRACT:

Background

Sexual transmission of human immunodeficiency virus (HIV) is inefficient and results in selection of viral variants based on incompletely understood factors. Functional variation in the Rev-Rev response element (RRE) regulatory axis of HIV affect replication kinetics and relative expression of viral proteins. We explored whether differences in this axis among viral isolates affect transmission fitness.

Methods

HIV sequences were identified from nine female-to-male transmission pairs. Using a rapid flow cytometric assay, we analyzed Rev-RRE functional activity of primary isolates.

Results

Rev-RRE activity was significantly lower in recipient viruses compared with corresponding donor viruses. In most transmission events, recipient virus Rev-RRE activity clustered at the extreme low end of the range of donor virus activity.

Conclusions

These data indicate selection pressure on the Rev-RRE axis during female-to-male sexual transmission. Variation in Rev-RRE activity may permit viral adaptation to different fitness landscapes and could play an important role in HIV pathogenesis.

SUBMITTER: Jackson PEH

PROVIDER: S-EPMC10580148 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rev-Rev Response Element Activity Selection Bias at the Human Immunodeficiency Virus Transmission Bottleneck.

Jackson Patrick E H PEH Holsey Jordan J Turse Lauren L Hammarskjold Marie-Louise ML Rekosh David D

Open forum infectious diseases 20230929 10

<h4>Background</h4>Sexual transmission of human immunodeficiency virus (HIV) is inefficient and results in selection of viral variants based on incompletely understood factors. Functional variation in the Rev-Rev response element (RRE) regulatory axis of HIV affect replication kinetics and relative expression of viral proteins. We explored whether differences in this axis among viral isolates affect transmission fitness.<h4>Methods</h4>HIV sequences were identified from nine female-to-male trans ...[more]

PMID: 37854107

Similar Datasets

Project description:UnlabelledHuman immunodeficiency virus (HIV) transmission typically results from infection by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly at random from the donor pool, or are they selected based on advantageous traits facilitating transmission? Finding evidence for selection during transmission is of particular interest, because it would indicate that phenotypic and/or genetic properties of the viruses might be harnessed as potential vaccine targets or immunotherapies. Here, we systematically evaluated the differences between the Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F variants in search of "signature" sites of transmission. We also surveyed residue preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed significant selection, and an additional two sites showed a similar trend. Therefore, the six sites clearly differentiate T/F viruses from the majority of circulating variants in the stocks. The selection of SIV/SHIV could be inferred reasonably across both vaccinated and unvaccinated subjects, with infections resulting from vaginal, rectal, and intravenous routes of transmission and regardless of viral dosage. The evidence for selection in SIV and SHIV T/F variants is strong and plentiful, and in HIV the evidence is suggestive though commensurate with the availability of suitable data for analysis. Two of the signature residues are completely conserved across the SIV, SHIV, and HIV variants we examined. Five of the signature residues map to the C1 region of gp120 and one to the signal peptide. Our data raise the possibility that C1, while governing the association between gp120 and gp41, modulates transmission efficiency, replicative fitness, and/or host cell tropism at the level of virus-cell attachment and entry.ImportanceThe present study finds significant evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data provide ancillary evidence suggesting the same sites are under selection in HIV. Our findings suggest that the signature residues are involved in increasing the transmissibility of infecting viruses; therefore, they are potential targets for developing a vaccine or other protective measures. A recent study identified the same T/F signature motif but interpreted it as an effect of neutralization resistance. Here, we show that the T/F motif has broader functional significance beyond neutralization sensitivity, because it is present in nonimmune subjects. Also, a vaccine regimen popular in animal trials might have increased the transmission of variants with otherwise low transmission fitness. Our observations might explain why many animal vaccine trials have not faithfully predicted outcomes in human vaccine trials and suggest that current practices in vaccine design need to be reexamined accordingly.

Dataset Information

Rev-Rev Response Element Activity Selection Bias at the Human Immunodeficiency Virus Transmission Bottleneck.

Background

Methods

Results

Conclusions

Publications

Rev-Rev Response Element Activity Selection Bias at the Human Immunodeficiency Virus Transmission Bottleneck.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets