HIV-1 integration landscape during latent and active infection

Lillian B. Cohn, Israel T. Silva, Thiago Y. Oliveira, Rafael A. Rosales, Erica H. Parrish, Gerald H. Learn, Beatrice H. Hahn, Julie L. Czartoski, M. Juliana McElrath, Clara Lehmann, Florian Klein, Marina Caskey, Bruce D. Walker, Janet D. Siliciano, Robert F. Siliciano, Mila Jankovic, Michel C. Nussenzweig

Research output: Contribution to journalArticlepeer-review

Abstract

Summary The barrier to curing HIV-1 is thought to reside primarily in CD4+ T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4+ T cells that remain relatively quiescent.

Original languageEnglish (US)
Pages (from-to)420-432
Number of pages13
JournalCell
Volume160
Issue number3
DOIs
StatePublished - Jan 29 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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