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. 2021 Nov 30;13(12):2398.
doi: 10.3390/v13122398.

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

Xiaolei Wang  1 , Widade Ziani  1 , Ronald S Veazey  1 , Huanbin Xu  1
Affiliations

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

Xiaolei Wang et al. Viruses. .

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.

Keywords: CD4+ T cell subsets; HIV/SIV; primary infection; viral reservoirs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cell-associated SIV RNA and DNA in peripheral and intestinal CD4+ T cells during primary SIV infection. (A) SIV RNA and DNA levels in CD4+ T cells sorted from blood and jejunum at the acute stage. (B) Correlation of SIV DNA with SIV DNA in peripheral and intestinal CD4+ T cells at the acute stage. Comparison of SIV RNA/DNA levels per 10e6 cell/equivalents in highly sorted CD4+ T cells as indicated. *, p < 0.05. NS, not significant. Note that there is no significant difference between peripheral blood and gut tissue.
Figure 2
Figure 2
SIV RNA and DNA levels in memory and naïve CD4+ T cells sorted from blood and intestinal tissues during primary SIV infection. Levels of SIV RNA (A) and SIV DNA (B) in CD4+ T cell subsets sorted from blood and jejunum at the acute stage. Note that significantly higher viral RNA/DNA levels were consistently detected in memory (CD95+) CD4+ T cells compared to naïve (CD95neg) cell subsets. Comparison of SIV RNA/DNA levels per 10e6 cell/equivalents in highly sorted CD4+ T cell subsets as indicated. *, p < 0.05. NS, not significant. Note that there is no significant difference between peripheral blood and gut tissue.
Figure 3
Figure 3
SIV RNA and DNA in CCR5-expressing memory CD4+ T cells sorted from blood and intestinal tissues during primary SIV infection. (A) Representative dot plot for cell sorting of CCR5+ or CCR5- memory CD4+ T cells, which was gated on CD3+ lymphocytes. SIV RNA (B) and SIV DNA (C) levels in CCR5+ or CCR5- memory CD4+ T cell subsets sorted from blood and jejunum at the acute stage. CCR5+ memory CD4+ T cells contain equivalent viral RNA/DNA to CCR5 negative cells in peripheral blood and jejunum. Comparison of SIV RNA/DNA levels per 10e6 cell/equivalents in highly sorted CD95+CCR5+ or CD95+CCR5-CD4+ T cell subsets as indicated. NS, not significant.
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