Multiple Origins of Virus Persistence during Natural Control of HIV Infection

Eli A. Boritz, Samuel Darko, Luke Swaszek, Gideon Wolf, David Wells, Xiaolin Wu, Amy R. Henry, Farida Laboune, Jianfei Hu, David Ambrozak, Marybeth S. Hughes, Rebecca Hoh, Joseph P. Casazza, Alexander Vostal, Daniel Bunis, Krystelle Nganou-Makamdop, James S. Lee, Stephen A. Migueles, Richard A. Koup, Mark ConnorsSusan Moir, Timothy Schacker, Frank Maldarelli, Stephen H. Hughes, Steven G. Deeks, Daniel C. Douek

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1004-1015
Number of pages12
JournalCell
Volume166
Issue number4
DOIs
StatePublished - Aug 11 2016

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