title: Strong human endogenous retrovirus-specific T cell responses are associated with control of HIV-1 in chronic infection.
abstract: Eight percent of the human genome is composed of human endogenous retroviruses (HERVs), which are thought to be inactive remnants of ancient infections. Previously, we showed that individuals with early HIV-1 infection have stronger anti-HERV T cell responses than uninfected controls. In this study, we investigated whether these responses persist in chronic HIV-1 infection and whether they have a role in the control of HIV-1. Peripheral blood mononuclear cells (PBMCs) from 88 subjects diagnosed with HIV-1 infection for at least 1 year (median duration of diagnosis, 13 years) were tested for responses against HERV peptides in gamma interferon (IFN-γ) enzyme immunospot (ELISPOT) assays. Individuals who control HIV-1 viremia without highly active antiretroviral therapy (HAART) had stronger and broader HERV-specific T cell responses than HAART-suppressed patients, virologic noncontrollers, immunologic progressors, and uninfected controls (P < 0.05 for each pairwise comparison). In addition, the magnitude of the anti-HERV T cell response was inversely correlated with HIV-1 viral load (r(2) = 0.197, P = 0.0002) and associated with higher CD4(+) T cell counts (r(2) = 0.072, P = 0.027) in untreated patients. Flow cytometric analyses of an HLA-B51-restricted CD8(+) HERV response in one HIV-1-infected individual revealed a less activated and more differentiated phenotype than that stimulated by a homologous HIV-1 peptide. HLA-B51 tetramer dual staining within this individual confirmed two different T cell populations corresponding to these HERV and HIV-1 epitopes, ruling out cross-reactivity. These findings suggest a possible role for anti-HERV immunity in the control of chronic HIV-1 infection and provide support for a larger effort to design an HIV-1 vaccine that targets conserved antigens such as HERV.
authors.affiliation: UCSF Division of Experimental Medicine, Building 3, Room 603, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, USA. Devi.SenGupta@ucsf.edu
authors.forename: Devi
authors.initials: D
authors.lastname: SenGupta
authors.forename: Ravi
authors.initials: R
authors.lastname: Tandon
authors.forename: Raphaella G S
authors.initials: RG
authors.lastname: Vieira
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.forename: Rachel
authors.initials: R
authors.lastname: Lown-Hecht
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Ormsby
authors.forename: Liyen
authors.initials: L
authors.lastname: Loh
authors.forename: R Brad
authors.initials: RB
authors.lastname: Jones
authors.forename: Keith E
authors.initials: KE
authors.lastname: Garrison
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: York
authors.forename: Gerald
authors.initials: G
authors.lastname: Spotts
authors.forename: Gustavo
authors.initials: G
authors.lastname: Reyes-Terán
authors.forename: Mario A
authors.initials: MA
authors.lastname: Ostrowski
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D020077:Endogenous Retroviruses / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag