Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection.
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.
Leligdowicz
Aleksandra
A
Medical Research Council Laboratories, Fajara, Republic of The Gambia. aleksandra.leligdowicz@balliol.ox.ac.uk
Yindom
Louis-Marie
LM
Onyango
Clayton
C
Sarge-Njie
Ramu
R
Alabi
Abraham
A
Cotten
Matthew
M
Vincent
Tim
T
da Costa
Carlos
C
Aaby
Peter
P
Jaye
Assan
A
Dong
Tao
T
McMichael
Andrew
A
Whittle
Hilton
H
Rowland-Jones
Sarah
S
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*