Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo.

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.

• Authors: Francesco R Simonetti, Michele D Sobolewski, Elizabeth Fyne, Wei Shao, Jonathan Spindler, Junko Hattori, Elizabeth M Anderson, Sarah A Watters, Shawn Hill, Xiaolin Wu, David Wells, Li Su, Brian T Luke, Elias K Halvas, Guillaume Besson, Kerri J Penrose, Zhiming Yang, Richard W Kwan, Carter Van Waes, Thomas Uldrick, Deborah E Citrin, Joseph Kovacs, Michael A Polis, Catherine A Rehm, Robert Gorelick, Michael Piatak, Brandon F Keele, Mary F Kearney, John M Coffin, Stephen H Hughes, John W Mellors, Frank Maldarelli
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 113 Issue 7 Pg. 1883-8 (Feb 16 2016) ISSN: 1091-6490 [Electronic] United States
• PMID: 26858442 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents

Topics

• Anti-HIV Agents (therapeutic use)
• CD4-Positive T-Lymphocytes (virology)
• HIV Infections (blood, drug therapy, virology)
• HIV-1 (pathogenicity, physiology)
• Humans
• Molecular Sequence Data
• Virulence
• Virus Replication