HLA-C increases HIV-1 infectivity and is associated with gp120

Abstract

Virionic HLA-C molecules associate to Env and increase the infectivity of both R5 and X4 viruses. Genetic polymorphisms associated to variations in HLA-C expression levels may therefore influence the individual viral set point not only by means of a regulation of the virus-specific immune response but also via a direct effect on the virus replicative capacity. These findings have implications for the understanding of the HIV-1 entry mechanism and of the role of Env conformational modifications induced by virion-associated host proteins.

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

“…Several evidences of the interaction between Env and HLA-C indicate that the presence of HLA-C is necessary to facilitate HIV-1 infection. The two molecules have been found associated and in the absence of HLA-C both fusion efficiency and virus infectivity are reduced345. In this work, a significant up-regulation of surface-HLA-C free chains, reactive to the L31 antibody18 was observed in HIV-1 chronically infected cells (ACH-2) following virus reactivation by TNF-α stimulation.…”

“…Previous studies demonstrated the association between Env and HLA-C34. To analyse Env and HLA-C interaction, the Bimolecular Fluorescence Complementation (BiFC) assay was exploited.…”

“…Previous results showed that HIV-1 envelope glycoprotein specifically associates with HLA-C, improving the ability of virions to infect target cells4. To discriminate the role of β 2 m in virion infectivity, Env-pseudotyped viruses (QHO and pRHPA) were produced in parental 293T and in CRISPR/Cas9 β 2 m negative 293T cells.…”

“…The specific association between HLA-C and Env has been confirmed in fusion complexes, where the recruitment of HLA-C molecules has been reported within CD4-CCR5-gp120/gp41 complexes, formed on cells during the process of HIV-1-induced cell-to-cell fusion4. The same study demonstrated that fusion efficiency is reduced in HLA-C negative cells and that pseudoviruses produced in HLA-C silenced cells are significantly less infectious than those produced in HLA-C expressing cells4. Another study demonstrated that HIV-1 infection of peripheral blood lymphocytes requires HLA-C expression, offering an explanation to the specific down-regulation of HLA-A and HLA-B, but not HLA-C, by HIV-1 Nef 5.…”

“…In addition, it was demonstrated that HLA-C induces changes in the viral envelope protein conformation, including an enhanced presentation of epitopes normally exposed upon CD4 binding3 and that HLA-C incorporation into HIV-1 virions reduces their susceptibility to neutralizing antibodies3. The specific association between HLA-C and Env has been confirmed in fusion complexes, where the recruitment of HLA-C molecules has been reported within CD4-CCR5-gp120/gp41 complexes, formed on cells during the process of HIV-1-induced cell-to-cell fusion4. The same study demonstrated that fusion efficiency is reduced in HLA-C negative cells and that pseudoviruses produced in HLA-C silenced cells are significantly less infectious than those produced in HLA-C expressing cells4.…”