Systemic and Intestinal Viral Reservoirs in CD4+ T Cell Subsets in Primary SIV Infection.

Xiaolei Wang,Ronald S. Veazey,Huanbin Xu,Widade Ziani

doi:10.3390/v13122398

Abstract

The HIV reservoir size in target CD4+ T cells during primary infection remains unknown. Here, we sorted peripheral and intestinal CD4+ T cells and quantified the levels of cell-associated SIV RNA and DNA in rhesus macaques within days of SIVmac251 inoculation. As a major target cell of HIV/SIV, CD4+ T cells in both tissues contained a large amount of SIV RNA and DNA at day 8–13 post-SIV infection, in which productive SIV RNA highly correlated with the levels of cell-associated SIV DNA. Memory CD4+ T cells had much higher viral RNA and DNA than naïve subsets, yet memory CD4+ T cells co-expressing CCR5 had no significant reservoir size compared with those that were CCR5-negative in blood and intestine. Collectively, memory CD4+ T cells appear to be the major targets for primary infection, and viral reservoirs are equally distributed in systemic and lymphoid compartments in acutely SIV-infected macaques.

Highlights

Subsets in Primary SIV Infection.The SIV/macaque model is the premier model used to examine early events in HIV infection
Macaques can be intravenously or mucosally challenged with precisely timed and defined doses of SIV, and tissues can be sampled at necropsy to definitively track the sequences and events in tissues of early SIV transmission and the establishment of infection. It was first shown in SIV-infected macaques, and later confirmed in HIV-infected humans, that the intestinal tract plays a fundamental role in the early events of HIV infection
Since the largest populations of activated memory CD4+ T cells reside in the intestinal tract in uninfected hosts, the early peak viral replication that occurs in primary infection is largely attributed to this massive viral replication in this vast pool of susceptible target cells in the gut

Summary

Introduction

Subsets in Primary SIV Infection.The SIV/macaque model is the premier model used to examine early events in HIV infection. Macaques can be intravenously or mucosally challenged with precisely timed and defined doses of SIV, and tissues can be sampled at necropsy to definitively track the sequences and events in tissues of early SIV transmission and the establishment of infection. It has been proposed that the productive infection and depletion of intestinal CD4+ T cells are accompanied by intestinal inflammation and the recruitment of additional target cells, supporting even more viral production, resulting in viral dissemination, intestinal CD4+ T cell depletion and the emergence of resistant viral variants that may evade the early immune responses to the transmitting founder viruses [4,5] To this end, early immune responses likely fail to clear the anatomical viral reservoirs. Defining the viral reservoirs in early infected CD4+ T cell subsets

Methods

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Discussion

Conclusion