Format

Send to

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

Multiple Origins of Virus Persistence during Natural Control of HIV Infection.

Author information

1
Human Immunology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
2
Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
3
Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
4
Thoracic and Gastrointestinal Oncology Branch, NCI, NIH, Bethesda, MD 20892, USA.
5
Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
6
Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892, USA.
7
Program in HIV Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
8
HIV Dynamics and Replication Program, NCI, NIH, Frederick, MD 21702, USA.
9
Human Immunology Section, Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA. Electronic address: ddouek@mail.nih.gov.

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.

PMID:
27453467
PMCID:
PMC4983216
DOI:
10.1016/j.cell.2016.06.039
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center