Abstract

We characterized the evolution of simian immunodeficiency virus (SIV) in the male genital tract by examining blood- and semen-associated virus from experimentally and sham vaccinated rhesus monkeys during primary infection. At the time of peak virus replication, SIV sequences were intermixed between the blood and semen supporting a scenario of high-level virus “spillover” into the male genital tract. However, at the time of virus set point, compartmentalization was apparent in 4 of 7 evaluated monkeys, likely as a consequence of restricted virus gene flow between anatomic compartments after the resolution of primary viremia. These findings suggest that SIV replication in the male genital tract evolves to compartmentalization after peak viremia resolves.

Highlights

  • An understanding of HIV-1 biology in the male genital tract will be central to understanding the transmission of this virus

  • While the transmission risk of HIV-1 has been associated with virus RNA levels in the peripheral blood of infected transmitting individuals, virus RNA levels in the blood only serve as a surrogate for the level of virus in ejaculate [1,3,4,5,6]

  • HIV-1 exists as a diverse population of related genetic variants that segregate into subpopulations within anatomic compartments of infected individuals [8,9]

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Summary

Introduction

An understanding of HIV-1 biology in the male genital tract will be central to understanding the transmission of this virus. During primary infection when HIV-1 transmission is high, virus levels in both the blood and the seminal plasma are both elevated [1,7]. During chronic infection blood and semen levels of HIV-1 can be discordant [1,7]. The intra-host compartmentalization of these variants has been documented in multiple anatomic regions including the peripheral blood, lungs, central nervous system, breast milk, gut and the female genital tract, [1,10,11,12,13,14,15,16]

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