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

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Science  01 Aug 2014:
Vol. 345, Issue 6196, pp. 570-573
DOI: 10.1126/science.1256304

A not-so-random integration for HIV

Even in the face of a cocktail of antiretroviral drugs, HIV manages to hang on. It does so by integrating its own genome into those of host cells, where it persists in a latent state. To better understand this process, Wagner et al. determined the sites where HIV integrated into three HIV-infected patients treated with antiretroviral drugs for more than a decade. They found an over-representation of sites where HIV integrated into genes associated with cancer and cell proliferation. Also, multiple cells in the same individual harbored the same integration sites. This suggests that integration into specific genes may drive cell proliferation and viral persistence.

Science, this issue p. 570


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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