Infection With HIV-2 Or HIV-1 – What Is The Difference?
There are two distinct, but related, HIV viruses that humans can become infected with — HIV-1 and HIV-2. Individuals infected with HIV-2 progress to AIDS at a dramatically reduced rate compared with individuals infected with HIV-1; in fact, most individuals infected with HIV-2 die of unrelated causes.
It is hoped that understanding why individuals infected with HIV-2 rarely progress to AIDS will help with the design of therapeutics and vaccine strategies for the treatment and prevention, respectively, of infection with HIV-1.
A new study by Aleksandra Leligdowicz and colleagues at the Weatherall Institute of Molecular Medicine, Oxford, demonstrates that individuals infected with HIV-2 mount a strong immune response to a specific region of the viral protein Gag.
The robustness of this response was inversely correlated with the amount of virus detected in the individual. In turn, individuals with high levels of detectable virus had fewer CD4+ T cells, indicating that they were progressing towards AIDS. The authors therefore suggest that T cell responses to Gag are important in determining the better outcome of infection with HIV-2 than infection with HIV-1.
J Clin Invest. 2007 Sep 6; [Epub ahead of print]
Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection.
Medical Research Council Laboratories, Fajara, Republic of The Gambia. Weatherall Institute of Molecular Medicine, Medical Research Council Human Immunology Unit, John Radcliffe Hospital, Oxford, United Kingdom. Projecto Saude Bandim, Bissau, Republic of Guinea-Bissau.
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.