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

2016; National Academy of Sciences; Volume: 113; Issue: 7 Linguagem: Inglês

10.1073/pnas.1522675113

1091-6490

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 W. Wells, Li Su, Brian T. Luke, Elias K. Halvas, Guillaume Besson, Kerri J. Penrose, Zhiming Yang, Richard Kwan, Carter Van Waes, Thomas S. Uldrick, Deborah E. Citrin, Joseph A. Kovacs, Michael A. Polis, Catherine Rehm, Robert J. Gorelick, Michael Piatak, Brandon F. Keele, Mary F. Kearney, John M. Coffin, Stephen H. Hughes, John W. Mellors, Frank Maldarelli,

Immune Cell Function and Interaction

Significance Reservoirs of HIV-infected cells persist during antiretroviral therapy, and understanding persistence is essential to develop HIV curative strategies. During replication, HIV integrates into the host genome; most proviruses are not infectious, but some with replication-competent HIV persist. Cells with integrated HIV can proliferate, potentially expanding the reservoir, but whether cells with replication-competent HIV actually undergo expansion is unknown. HIV reactivation is often lethal to infected cells, and others have reported finding no replication-competent HIV in expanded populations. We describe a highly expanded clone containing infectious HIV that was the source of viremia for years in a patient. Clonally expanded populations can represent a long-lived reservoir of HIV. Curative strategies will require targeting this persistence mechanism.