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

by Anderson, Elizabeth M. , Yang, Zhiming , Sobolewski, Michele D. , Fyne, Elizabeth , Keele, Brandon F. , Uldrick, Thomas , Shao, Wei , Gorelick, Robert , Wu, Xiaolin , Kovacs, Joseph , Hattori, Junko , Wells, David , Penrose, Kerri J. , Mellors, John W. , Hill, Shawn , Kwan, Richard W. , Rehm, Catherine A. , Citrin, Deborah E. , Halvas, Elias K. , Van Waes, Carter , Piatak, Michael , Maldarelli, Frank , Kearney, Mary F. , Hughes, Stephen H. , Simonetti, Francesco R. , Luke, Brian T. , Coffin, John M. , Spindler, Jonathan , Polis, Michael A. , Su, Li , Besson, Guillaume , Watters, Sarah A.

in Anti-HIV Agents - therapeutic use / Antiretroviral agents / Antiretroviral drugs / Biological Sciences / Cancer / CD4-Positive T-Lymphocytes - virology / Deoxyribonucleic acid / DNA / HIV / HIV Infections - blood / HIV Infections - drug therapy / HIV Infections - virology / HIV-1 - pathogenicity / HIV-1 - physiology / Human immunodeficiency virus / Human immunodeficiency virus 1 / Humans / Lentivirus / Medical Sciences / Metastasis / Molecular Sequence Data / Retroviridae / T cell receptors / Virulence / Virus Replication

2016

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2016

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2016

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Journal Article

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

Anderson, Elizabeth M.,

Yang, Zhiming,

Sobolewski, Michele D.,

Fyne, Elizabeth,

Keele, Brandon F.,

Uldrick, Thomas,

Shao, Wei,

Gorelick, Robert,

Wu, Xiaolin,

Kovacs, Joseph,

Hattori, Junko,

Wells, David,

Penrose, Kerri J.,

Mellors, John W.,

Hill, Shawn,

Kwan, Richard W.,

Rehm, Catherine A.,

Citrin, Deborah E.,

Halvas, Elias K.,

Van Waes, Carter,

Piatak, Michael,

Maldarelli, Frank,

Kearney, Mary F.,

Hughes, Stephen H.,

Simonetti, Francesco R.,

Luke, Brian T.,

Coffin, John M.,

Spindler, Jonathan,

Polis, Michael A.,

Su, Li,

Besson, Guillaume,

Watters, Sarah A.

2016

Overview

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.

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Publisher

National Academy of Sciences

Subject

Anti-HIV Agents - therapeutic use

/ Antiretroviral agents

/ Antiretroviral drugs

/ Biological Sciences

/ Cancer

/ CD4-Positive T-Lymphocytes - virology

/ Deoxyribonucleic acid