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HIV-1 Env associates with HLA-C free-chains at the cell membrane modulating viral infectivity

Michela Serena1, Francesca Parolini1, Priscilla Biswas2

  • 1Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.

Scientific Reports
|January 5, 2017
PubMed

Insights

Human Leukocyte Antigen-C (HLA-C) interacts with HIV-1 envelope glycoprotein (Env), enhancing viral infectivity. This study reveals that HIV-1 specifically increases free HLA-C chains, crucial for this interaction and increased infectivity.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Human Leukocyte Antigen-C (HLA-C) is known to associate with HIV-1 envelope glycoprotein (Env).
  • Virions lacking HLA-C exhibit reduced infectivity and increased susceptibility to neutralizing antibodies.
  • HLA-C, like other MHC-I molecules, requires β2-microglobulin (β2m) for proper folding and cell surface expression, though its association with β2m is weaker, leading to free HLA-C chains.

Purpose of the Study:

  • To investigate the specific role of HLA-C free chains in HIV-1 infectivity.
  • To elucidate the mechanism by which HIV-1 interacts with HLA-C at the cell membrane.
  • To understand how the association with β2m influences HLA-C's function in HIV-1 infection.

Main Methods:

  • Analysis of HLA-C and β2m expression on HIV-1 infected cells.
  • Production of HIV-1 Env-pseudotyped viruses in the presence and absence of β2m.
  • Assessment of viral infectivity and antibody susceptibility.

Main Results:

  • HIV-1 infection increases the abundance of HLA-C free chains on the cell membrane.
  • The association between Env and HLA-C occurs at the cell membrane and requires β2m.
  • Enhanced HIV-1 infectivity mediated by HLA-C involves HLA-C free chains correctly assembled with β2m.
  • Viruses produced without β2m show reduced infectivity.

Conclusions:

  • HIV-1 specifically upregulates HLA-C free chains, which are critical for enhanced viral infectivity.
  • The interaction between Env and HLA-C free chains at the cell membrane, dependent on β2m, facilitates HIV-1 entry.
  • The binding stability of HLA-C to β2m may determine its dual role as an immune molecule and an accessory molecule in HIV-1 infection.

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