Journal article

Compartmentalization and Clonal Amplification of HIV-1 in the Male Genital Tract Characterized Using Next-Generation Sequencing


Research Areas

Publication Details

Author list: Kariuki SM, Selhorst P, Anthony C, Matten D, Abrahams MR, Martin DP, Ariën KK, Rebe K, Williamson C, Dorfman JR

Publisher: American Society for Microbiology

Publication year: 2020

Journal: Journal of Virology

Journal acronym: JVI

Volume number: 94

Issue number: 12

Start page: 1

End page: 18

Total number of pages: 18

ISSN: 0022-538X

eISSN: 1098-5514

URL: https://jvi.asm.org/content/94/12/e00229-20


Abstract

Compartmentalization of HIV-1 between the systemic circulation and the male genital tract may have a substantial impact on which viruses are available for sexual transmission to new hosts. We studied compartmentalization and clonal amplification of HIV-1 populations between blood and the genital tract from ten antiretroviral-naive men using Illumina MiSeq with a PrimerID approach. We found evidence of some degree of compartmentalization in every study participant, unlike previous reports, which collectively show that only ~50% of analyzed individuals exhibit compartmentalization of HIV-1 lineages between the male genital tract and blood. Using down-sampling simulations, we determined that this disparity can be explained by differences in sampling depth in that, had we sequenced to a lower depth, we would also have found compartmentalization in only ~50% of the study participants. For most study participants, phylogenetic trees were rooted in blood, suggesting that the male genital tract reservoir is seeded by incoming variants from the blood. Clonal amplification was observed in all study participants and was a characteristic of both blood and semen viral populations. We also show evidence for independent viral replication in the genital tract in the individual with the most severely compartmentalized HIV-1 populations. The degree of clonal amplification was not obviously associated with the extent of compartmentalization. We were also unable to detect any association between history of sexually transmitted infections and level of HIV-1 compartmentalization. Overall, our findings contribute to a better understanding of the dynamics that affect the composition of virus populations that are available for transmission.

​​​​​​​Importance

Within an individual living with HIV-1, factors that restrict the movement of HIV-1 between different compartments – such as between the blood and the male genital tract - could strongly influence which viruses reach sites in the body from which they can be transmitted. Using deep sequencing, we found strong evidence of restricted HIV-1 movements between the blood and genital tract of all ten men that we studied. We additionally found that neither the degree to which particular genetic variants of HIV-1 proliferate (in blood or genital tract), nor an individual’s history of sexually transmitted infections, detectably influenced the degree to which virus movements were restricted between the blood and genital tract. Last, we show evidence that viral replication gave rise to a large clonal amplification in semen in a donor with highly compartmentalized HIV-1 populations, raising the possibility that differential selection of HIV-1 variants in the genital tract may occur.


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Keywords

HIV-1, HIV Phylogenetics


Last updated on 2020-09-10 at 12:26