Publications

Authors:

Parolini, Francesca; Biswas, Priscilla; Serena, Michela; Sironi, Francesca; Muraro, Valentina; Guizzardi, Elisabetta; Cazzoletti, Lucia; Scupoli, Maria; Gibellini, Davide; Ugolotti, Elisabetta; Biassoni, Roberto; Beretta, Alberto; Malnati, Mauro; Romanelli, Maria; Zipeto, Donato

Title:

Stability and expression levels of HLA-C on the cell membrane modulate HIV-1 infectivity

Year:

2018

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

Journal of Virology

ISSN of journal:

0022-538X

N° Volume:

92

Number or Folder:

1

Page numbers:

JVI.01711-17-.17 pages

Keyword:

HLA-C; HIV-1 control; viral infectivity modulation; HLA-C expression levels; HLA-C heterotrimers stability

Short description of contents:

HLA-C expression is associated with a differential ability to control HIV-1 infection. Higher HLA-C levels may lead to a better control of HIV-1 infection through both a higher efficiency of antigen presentation to cytotoxic T lymphocytes (CTLs), as well as the triggering of activating Killer Immunoglobulin like receptors (KIR) on NK-cells, whereas lower levels may provide a poor HIV-1 control and a rapid progression toward AIDS.We characterized the relative amount of HLA-C heterotrimers (heavy chain/β2m/peptide) and HLA-C free heavy chains on PBMC from healthy blood donors harboring both alleles with stable or unstable binding to β2m/peptide. We analyzed the stability of HLA-C heterotrimers of different allotypes and the infectivity of HIV-1 virions produced by PBMC with various allotypes.We observed significant differences in HLA-C heterotrimers stability and in expression levels. We found that R5 HIV-1 virions produced by PBMC harboring unstable HLA-C alleles were more infectious than those produced by PBMC carrying the stable variants.We propose that HIV-1 infectivity might depend both on the amounts of HLA-C molecules and on their stability as trimeric complex. According to this model, individuals with low expressed HLA-C alleles and unstable binding to β2m/peptide might have a worse control of HIV-1 infection and an intrinsically higher capacity to support viral replication.IMPORTANCE 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.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.This study provides new information that could be useful to design novel vaccine strategies and therapeutic approaches against HIV-1.

Web page:

https://doi.org/10.1128/JVI.01711-17

Product ID:

99933

Handle IRIS:

11562/971868

Last Modified:

November 15, 2022

Bibliographic citation:

Parolini, Francesca; Biswas, Priscilla; Serena, Michela; Sironi, Francesca; Muraro, Valentina; Guizzardi, Elisabetta; Cazzoletti, Lucia; Scupoli, Maria; Gibellini, Davide; Ugolotti, Elisabetta; Biassoni, Roberto; Beretta, Alberto; Malnati, Mauro; Romanelli, Maria; Zipeto, Donato, Stability and expression levels of HLA-C on the cell membrane modulate HIV-1 infectivity «Journal of Virology» , vol. 92 , n. 1 , 2018 , pp. JVI.01711-17-.17 pages

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