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

J Acquir Immune Defic Syndr. 2016 Apr 1;71(4):353-8. doi: 10.1097/QAI.0000000000000890.

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 Ki67CCR5CD4T 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Proliferation
  • Colon / cytology*
  • Colon / virology
  • Female
  • Macaca mulatta
  • Male
  • RNA, Viral / blood
  • Rectum / cytology*
  • Rectum / virology
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus*
  • T-Lymphocytes / classification*
  • T-Lymphocytes / physiology
  • Time Factors
  • Viral Load
  • Virus Replication / physiology*

Substances

  • RNA, Viral