What is it about?

Following HIV-1 infection, some people advance rapidly toward AIDS while others have a slow disease progression. HLA-C, a molecule involved in immunity, is a key determinant of HIV-1 control.

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Why is it important?

Here we reveal how HLA-C variants contribute to modulate viral infectivity. HLA-C is present on the cell surface in two different conformations: the immunologically active conformation is part of a complex that includes β2-microglobulin/peptide; the other conformation is not bound to β2-microglobulin/peptide and can associate with HIV-1, increasing its infectivity. Individuals with HLA-C variants with a predominance of immunologically active conformations would display a stronger immunity against HIV-1, a reduced viral infectivity and an effective control of HIV-1 infection, while subjects with HLA-C variants that easily dissociate from β2-microglobulin/peptide would have a reduced immunological response to HIV-1 and produce more infectious virions.

Perspectives

This study provides new information that could be useful to design novel vaccine strategies and therapeutic approaches against HIV-1. HLA-C variants which may more easily dissociate, will likely present a higher proportion of free heavy chains increasing HIV-1 infectivity and promoting β2m release, contributing to inflammatory states. Studies published in the early years of HIV-1 pandemic reported that patients with HIV-1 dementia presented a higher concentration of β2m in cerebrospinal fluid that β2m levels were raised in serum of AIDS-related-complex patients and during HIV-1 infection progression. Our results start to shed some light on these never fully explained observations: individuals with Unstable HLA-C alleles might lose β2m leading to its accumulation in serum and in the cerebrospinal fluid.

Donato Zipeto
University of Verona

Read the Original

This page is a summary of: Stability and Expression Levels of HLA-C on the Cell Membrane Modulate HIV-1 Infectivity, Journal of Virology, October 2017, ASM Journals,
DOI: 10.1128/jvi.01711-17.
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