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Effective HIV control may depend on viral protein targeted by immune cells

d be destroyed. Earlier studies, including a 2004 Nature report from the same group, showed that the genetically determined version of an individual’s HLA Class I molecules could strongly influence immune control of HIV.

The current study found that only CD8 responses against the Gag protein were associated with significantly reduced viral levels and that individuals with responses against several different Gag fragments had even lower viral loads. In contrast, those with stronger responses against other HIV proteins ?including Env, a protein that is the focus of several vaccine studies ?had higher viral levels indicating poorer control of HIV.

In people receiving no antiretroviral treatment, the improved HIV control associated with Gag-specific CD8 response would probably translate into asymptomatic infection for more than a decade, compared with progression to AIDS within two to three years of infection in those with no Gag responses. The reason why patients?particular HLA Class I molecules are linked to different HIV disease outcomes now appears to be related to the number of Gag fragments displayed by different versions of the Class I molecule.

Mechanisms underlying the different effects of the protein-specific immune responses are unknown and require further investigation. The researchers suggest that responses against proteins like Env might be inherently less effective or might only be generated in response to elevated viral loads. Therefore, the findings of this study, which reflect chronic HIV infection, might not apply in situations in which vaccination generates an immune response before infection occurs.

"The possibility that there may be fundamental differences between the impact of Gag and non-Gag CD8 responses on the ability to control HIV has clear relevance to vaccine development," says Goulder, who is an associate professor of Medicine at Harvard Medical School.
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Source:Massachusetts General Hospital


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