Author:
Simonetti Francesco R.,Sobolewski Michele D.,Fyne Elizabeth,Shao Wei,Spindler Jonathan,Hattori Junko,Anderson Elizabeth M.,Watters Sarah A.,Hill Shawn,Wu Xiaolin,Wells David,Su Li,Luke Brian T.,Halvas Elias K.,Besson Guillaume,Penrose Kerri J.,Yang Zhiming,Kwan Richard W.,Van Waes Carter,Uldrick Thomas,Citrin Deborah E.,Kovacs Joseph,Polis Michael A.,Rehm Catherine A.,Gorelick Robert,Piatak Michael,Keele Brandon F.,Kearney Mary F.,Coffin John M.,Hughes Stephen H.,Mellors John W.,Maldarelli Frank
Abstract
Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4+T cells. Some of these CD4+T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4+ T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1–infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4+T cells can be a reservoir of infectious HIV-1.
Funder
HHS | NIH | National Cancer Institute
Publisher
Proceedings of the National Academy of Sciences
Cited by
283 articles.
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