Multiple Origins of Virus Persistence during Natural Control of HIV Infection

Cell. 2016 Aug 11;166(4):1004-1015. doi: 10.1016/j.cell.2016.06.039. Epub 2016 Jul 21.

Abstract

Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites, and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood / virology
  • CD4-Positive T-Lymphocytes / immunology
  • Chronic Disease
  • DNA, Viral / genetics
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Leukocytes, Mononuclear
  • Lymph Nodes / virology
  • Proviruses / immunology
  • Sequence Analysis, DNA
  • Virus Physiological Phenomena
  • Virus Replication

Substances

  • DNA, Viral