Early SIV Dissemination After Intrarectal SIVmac251 Challenge Was Associated With Proliferating Virus-Susceptible Cells in the Colorectum


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Abstract

Objective:Few studies have examined the eclipse time of simian immunodeficiency virus/HIV infection through the anal route. We aimed to measure the eclipse time after SIVmac251 intrarectal inoculation, and to investigate the factor(s) associated with early dissemination.Design:Forty macaques were intrarectally challenged with SIVmac251 3 times at 2-week intervals.Methods:Plasma viral RNA was monitored at 4, 7, 11, 14, 21, and 28 days after infection. Rectal/vaginal tissues were obtained and tissue viral loads (VLs) were measured at day 14 postinfection.Results:Of 40 macaques 26 (65%) had first detectable viral RNAs in the plasma at day 7 after the challenge that led to productive infection. Strikingly, 6 animals (15%) had detectable viral RNA in the plasma as early as at day 4. The Ki67+ viral target CD4+ T cells in the colorectal tissues were significantly higher in the early or middle-transmitter groups than those in the late-transmitter group. The rectal VL did not correlate with plasma VL at 14-day postinoculation, but did positively correlate with plasma VLs at days 21 and 28 postinfection.Conclusions:The median eclipse time after intrarectal challenge was 7 days, with a few early transmitters at 4 days. More rapid viral dissemination was associated with a high frequency of colorectal Ki67+CCR5+CD4+T cells, which fuel the local viral replication. Furthermore, local viral replication in the colorectal tissue during the early stage might affect the plasma VL in a delayed manner. Therefore, to reduce/limit these target cells at the portal of viral entry is essential.

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