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Maldarelli, F.; Wu, X.; Su, L.; Simonetti, F. R.; Shao, W.; Hill, S.; Spindler, J.; Ferris, A. L.; Mellors, J. W.; Kearney, M. F.; Coffin, J. M.; Hughes, S. H.
Science (American Association for the Advancement of Science), 07/2014, Volume: 345, Issue: 6193Journal Article
The persistence of HIV-infected cells in individuals on suppressive combination antiretroviral therapy (cART) presents a major barrier for curing HIV infections. HIV integrates its DNA into many sites in the host genome; we identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on cART. About 40% of the integrations were in clonally expanded cells. Approximately 50% of the infected cells in one patient were from a single clone, and some clones persisted for many years. There were multiple independent integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. Our findings show that HIV integration sites can play a critical role in expansion and persistence of HIV-infected cells.
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