Research Article

Specific HIV integration sites are linked to clonal expansion and persistence of infected cells

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Science  11 Jul 2014:
Vol. 345, Issue 6193, pp. 179-183
DOI: 10.1126/science.1254194

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For HIV: Location, location, location

HIV-infected cells linger even in the face of therapy, and this persistence, termed the latent reservoir, is a major hurdle for curing HIV. HIV integrates itself into the DNA of its host cells. Could that affect the latent reservoir? To find out, Maldarelli et al. drew blood from five HIV patients on antiretroviral therapy and analyzed sites where HIV had inserted itself into the blood cells' DNA (see the Perspective by Margolis and Bushman). In many cases, these sites were not random; HIV often weaseled its way into genes that help cells grow and proliferate. Where HIV integrates into the host genome may thus determine the size of the latent reservoir.

Science, this issue p. 179; see also p. 143


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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