Wagner TA, McLaughlin S, Garg K, Cheung CY, Larsen BB, Styrchak S, Huang HC, Edlefsen PT, Mullins JI, Frenkel LM (2014). HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science (New York, N.Y.), 345(6196), 570-3. (pubmed) (doi)
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.
Correction (originally made in Science on 21 October 2015, first noted here on 10 February 2016): Table S3 has been revised. A section of one column of the originally published table was sorted incorrectly so that a subset of the chromosomal coordinates did not match the gene or sequence they were assigned. The original version is still accessible as:1256304WagnerTableS3.xlsx