Gag-positive reservoir cells are susceptible to HIV-specific cytotoxic T lymphocyte mediated clearance in vitro and can be detected in vivo [corrected]

• Published in: PloS one 2013-08, Vol.8 (8), p.e71879-e71879
• Main Authors: Graf, Erin H, Pace, Matthew J, Peterson, Bennett A, Lynch, Lindsay J, Chukwulebe, Steve B, Mexas, Angela M, Shaheen, Farida, Martin, Jeffrey N, Deeks, Steven G, Connors, Mark, Migueles, Stephen A, O'Doherty, Una
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Antiretroviral drugs; Antiviral agents; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cells, Cultured; Coculture Techniques; Controllers; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA, Viral - genetics; Drug therapy; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - immunology; gag Gene Products, Human Immunodeficiency Virus - metabolism; Gag protein; Health aspects; HIV; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - metabolism; Human immunodeficiency virus; Humans; Immune clearance; Immune response; In vivo methods and tests; Infections; Laboratories; Lymphocytes; Lymphocytes T; Medicine; Pathology; Protein expression; Proteins; Real-Time Polymerase Chain Reaction; Robust control; T cells; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - virology; Therapy; Vaccination; Viral proteins; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0071879

Resting CD4+T cells infected with HIV persist in the presence of suppressive anti-viral therapy (ART) and are barriers to a cure. One potential curative approach, therapeutic vaccination, is fueled by recognition of the ability of a subset of elite controllers (EC) to control virus without therapy due to robust anti-HIV immune responses. Controllers have low levels of integrated HIV DNA and low levels of replication competent virus, suggesting a small reservoir. As our recent data indicates some reservoir cells can produce HIV proteins (termed GPR cells for Gag-positive reservoir cells), we hypothesized that a fraction of HIV-expressing resting CD4+T cells could be efficiently targeted and cleared in individuals who control HIV via anti-HIV cytotoxic T lymphocytes (CTL). To test this we examined if superinfected resting CD4+T cells from EC express HIV Gag without producing infectious virus and the susceptibility of these cells to CTL. We found that resting CD4+T cells expressed HIV Gag and were cleared by autologous CD8+T cells from EC. Importantly, we found the extent of CTL clearance in our in vitro assay correlates with in vivo reservoir size and that a population of Gag expressing resting CD4+T cells exists in vivo in patients well controlled on therapy.