title: Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection.
abstract: HIV-2 infection in the majority of infected subjects follows an attenuated disease course that distinguishes it from infection with HIV-1. Antigen-specific T cells are pivotal in the management of chronic viral infections but are not sufficient to control viral replication in HIV-1-positive subjects, and their function in HIV-2 infection is not fully established. In a community-based cohort of HIV-2 long-term nonprogressors in rural Guinea-Bissau, we performed what we believe is the first comprehensive analysis of HIV-2-specific immune responses. We demonstrate that Gag is the most immunogenic protein. The magnitude of the IFN-gamma immune response to the HIV-2 proteome was inversely correlated with HIV-2 viremia, and this relationship was specifically due to the targeting of Gag. Furthermore, patients with undetectable viremia had greater Gag-specific responses compared with patients with high viral replication. The most frequently recognized peptides clustered within a defined region of Gag, and responses to a single peptide in this region were associated with low viral burden. The consistent relationship between Gag-specific immune responses and viremia control suggests that T cell responses are vital in determining the superior outcome of HIV-2 infection. A better understanding of how HIV-2 infection is controlled may identify correlates of effective protective immunity essential for the design of HIV vaccines.
authors.affiliation: Medical Research Council Laboratories, Fajara, Republic of The Gambia. aleksandra.leligdowicz@balliol.ox.ac.uk
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Leligdowicz
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Yindom
authors.forename: Clayton
authors.initials: C
authors.lastname: Onyango
authors.forename: Ramu
authors.initials: R
authors.lastname: Sarge-Njie
authors.forename: Abraham
authors.initials: A
authors.lastname: Alabi
authors.forename: Matthew
authors.initials: M
authors.lastname: Cotten
authors.forename: Tim
authors.initials: T
authors.lastname: Vincent
authors.forename: Carlos
authors.initials: C
authors.lastname: da Costa
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015498:HIV-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D020543:Proteome / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014766:Viremia / Q000276:immunology*