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Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections

Jason M. Brenchley, Carol Vinton, Brian Tabb, Xing Pei Hao, Elizabeth Connick, Mirko Paiardini, Jeffrey D. Lifson, Guido Silvestri, Jacob D. Estes
This article has an Erratum 123(26):4152

Abstract

Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a non-resolving chronic infection, but do not develop AIDS. Mechanisms to explain the nonprogressive nature of SIV infection in natural hosts that underlie maintained high levels of plasma viremia without apparent loss of target cells remain unclear. Here, we used comprehensive approaches (i.e. FACS sorting, qRT-PCR, immunohistochemistry, and in situ hybridization) to study viral infection within subsets of peripheral blood and lymphoid tissue (LT) CD4+ T cells in cohorts of chronically SIV-infected rhesus macaques (RM), HIV-infected humans and SIVsmm-infected sooty mangabeys (SM). We find: (1) infection frequencies among CD4+ T cells in chronically SIV-infected RM are significantly higher than those in SIVsmm-infected SM; (2) infected cells are found in distinct anatomical LT niches and different CD4+ T cell subsets in SIV-infected RM and SM, with infection patterns of RM reflecting HIV infection in humans; (3) TFH cells are infected at higher frequencies in RM and humans than in SM and; (4) LT viral burden, including follicular dendritic cell deposition of virus, is increased in RM and humans compared to SM. These data provide insights into how natural hosts are able to maintain high levels of plasma viremia while avoiding development of immunodeficiency.

  • Submitted June 18, 2012.
  • Accepted August 31, 2012.