| Literature DB >> 26858442 |
Francesco R Simonetti1, Michele D Sobolewski2, Elizabeth Fyne2, Wei Shao3, Jonathan Spindler4, Junko Hattori4, Elizabeth M Anderson4, Sarah A Watters4, Shawn Hill4, Xiaolin Wu3, David Wells3, Li Su3, Brian T Luke3, Elias K Halvas2, Guillaume Besson2, Kerri J Penrose2, Zhiming Yang5, Richard W Kwan6, Carter Van Waes7, Thomas Uldrick8, Deborah E Citrin9, Joseph Kovacs10, Michael A Polis6, Catherine A Rehm6, Robert Gorelick11, Michael Piatak11, Brandon F Keele11, Mary F Kearney4, John M Coffin12, Stephen H Hughes4, John W Mellors2, Frank Maldarelli13.
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.Entities:
Keywords: HIV persistence; clonal expansion of infected cells; replication-competent HIV
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Year: 2016 PMID： 26858442 PMCID： PMC4763755 DOI： 10.1073/pnas.1522675113
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205