Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Jason M. Brenchley1,
  2. Carol Vinton2,
  3. Brian Tabb3,
  4. Xing Pei Hao4,
  5. Elizabeth Connick5,
  6. Mirko Paiardini6,
  7. Jeffrey D. Lifson3,
  8. Guido Silvestri6, and
  9. Jacob D. Estes3,*
  1. 1 Program in Barrier Immunity and Repair and Immunopathogenesis Unit, Lab of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States;
  2. 2 Lab of Molecular Microbiology, NIAID, NIH, Bethesda, MD, United States;
  3. 3 AIDS and Cancer Virus Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States;
  4. 4 Pathology and Histotechnology Laboratory, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, United States;
  5. 5 Division of Infectious Diseases, University of Colorado Denver, Aurora, CO, United States;
  6. 6 Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States
  1. * Corresponding author; email: estesj{at}mail.nih.gov
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.