Early SIV Dissemination After Intrarectal SIVmac251 Challenge Was Associated With Proliferating Virus-Susceptible Cells in the Colorectum. (1st April 2016)

• Record Type: Journal Article
• Authors: Sui, Yongjun; Lee, Eun Mi; Wang, Yichuan; Hogg, Alison; Frey, Blake; Venzon, David; Pal, Ranajit; Berzofsky, Jay A.
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 71:Number 4(2016)
• Publication Date: 2016-04-01
• Subjects: eclipse time -- intrarectal inoculation -- SIV -- viral loads -- viral target cells -- AIDS virus transmission; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/QAI.0000000000000890
• Languages: English
• ISSNs: 1525-4135

Abstract

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. Abstract : Supplemental Digital Content is Available in the Text.