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HIV Infected T Cells Can Proliferate in vivo Without Inducing Expression of the Integrated Provirus

2019; Frontiers Media; Volume: 10; Linguagem: Inglês

10.3389/fmicb.2019.02204

1664-302X

Andrew Musick, Jonathan Spindler, Eli Boritz, Liliana Pérez, Daniel Crespo-Vélez, Sean C. Patro, Michele D. Sobolewski, Michael J. Bale, Carolyn Reid, Brandon F. Keele, Adam A. Capoferri, Wei Shao, Ann Wiegand, Francesco R. Simonetti, John W. Mellors, Stephen H. Hughes, John M. Coffin, Frank Maldarelli, Mary F. Kearney,

Cytomegalovirus and herpesvirus research

HIV-1 proviruses can persist during ART in clonally-expanded populations of CD4+ T cells. To date, few examples of an expanded clones containing replication-competent proviruses exist, although it is suspected to be common. One such clone, denoted AMBI-1 (Maldarelli et al., 2014), was also a source of persistent viremia on ART, begging the question of how the AMBI-1 clone can survive despite infection with a replication-competent, actively-expressing provirus. We hypothesized that only a small fraction of cells within the AMBI-1 clone are activated to produce virus particles during cell division while the majority remain latent despite division, ensuring their survival. To address this question, we determined the fraction of HIV-1 proviruses within the AMBI-1 clone that expresses unspliced cell-associated RNA during ART and compared this fraction to 33 other infected T cell clones within the same individual.