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

F Maldarelli, X Wu, L Su, FR Simonetti, W Shao, S Hill… - Science, 2014 - science.org
F Maldarelli, X Wu, L Su, FR Simonetti, W Shao, S Hill, J Spindler, AL Ferris, JW Mellors…
Science, 2014science.org
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 …
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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