@article{ccc47ef6d34e4c78a8e44c3c7c997056,
title = "HIV-1 integration landscape during latent and active infection",
abstract = "Summary The barrier to curing HIV-1 is thought to reside primarily in CD4+ T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4+ T cells that remain relatively quiescent.",
author = "Cohn, {Lillian B.} and Silva, {Israel T.} and Oliveira, {Thiago Y.} and Rosales, {Rafael A.} and Parrish, {Erica H.} and Learn, {Gerald H.} and Hahn, {Beatrice H.} and Czartoski, {Julie L.} and McElrath, {M. Juliana} and Clara Lehmann and Florian Klein and Marina Caskey and Walker, {Bruce D.} and Siliciano, {Janet D.} and Siliciano, {Robert F.} and Mila Jankovic and Nussenzweig, {Michel C.}",
note = "Funding Information: We would like to acknowledge all patients who contributed to this study. We thank Qiao Wang for invaluable discussions; Johannes Scheid for the coordination and preparation of viremic controller samples; Joshua Horwitz for samples during the initial development of integration sequencing; Klara Velinzon and Gaelle Breton for FACSorting; Zoran Jankovic for laboratory support; Rockefeller Genomics Resource Center and New York Genome Center for sequencing; David Chambliss for assistance in obtaining human samples; Arlene Hurley and Gisela Kremer for assistance in patient coordination; and all members of Nussenzweig and Mucida labs for valuable discussion and advice. This work was supported in part by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery Grant OPP 1033115 (to M.C.N.) and CHAVI-ID Award UM1AI100663. This work was also supported in part by grant #8 UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. E.H.P., G.H.L., and B.H.H. are supported by UM1 AI100645 and R37 AI 066998. M.C.N., R.F.S., and B.D.W. are Howard Hughes Medical Institute Investigators. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = jan,
day = "29",
doi = "10.1016/j.cell.2015.01.020",
language = "English (US)",
volume = "160",
pages = "420--432",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}