Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection

TA Wagner, S McLaughlin, K Garg, CYK Cheung… - Science, 2014 - science.org
TA Wagner, S McLaughlin, K Garg, CYK Cheung, BB Larsen, S Styrchak, HC Huang…
Science, 2014science.org
Antiretroviral treatment (ART) of HIV infection suppresses viral replication. Yet if ART is
stopped, virus reemerges because of the persistence of infected cells. We evaluated the
contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. A
total of 534 HIV integration sites (IS) and 63 adjacent HIV env sequences were derived from
three study participants over 11.3 to 12.7 years of ART. Each participant had identical viral
sequences integrated at the same position in multiple cells, demonstrating infected-cell …
Antiretroviral treatment (ART) of HIV infection suppresses viral replication. Yet if ART is stopped, virus reemerges because of the persistence of infected cells. We evaluated the contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. A total of 534 HIV integration sites (IS) and 63 adjacent HIV env sequences were derived from three study participants over 11.3 to 12.7 years of ART. Each participant had identical viral sequences integrated at the same position in multiple cells, demonstrating infected-cell proliferation. Integrations were overrepresented in genes associated with cancer and favored in 12 genes across multiple participants. Over time on ART, a greater proportion of persisting proviruses were in proliferating cells. HIV integration into specific genes may promote proliferation of HIV-infected cells, slowing viral decay during ART.
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