A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1

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CD4bs is a central viral vulnerability site and isolation of new anti-HIV-1 CD4bs broadly neutralizing antibodies (bNAbs) provides information about viral escape mechanisms. Here we describe a new anti-HIV-1 bNAb that was isolated from an HIV-1 infected donor. The antibody, 179NC75, targets the CD4 binding site in a glycan-dependent manner. Although many CD4bs antibodies have been already described, a glycan-dependent mode of recognition is unusual for anti-HIV-1 CD4bs bNAbs. The glycan-dependent CD4bs antibodies have never been tested for their ability to neutralize HIV-1 in vivo. We infected humanized mice with HIV-1YU2 and treated them with 179NC75 three weeks after infection. We observed a drop in viral load immediately after treatment followed by a viral rebound. The viral rebound was associated with specific escape mutations in the plasma virus envelope, resulting in a deletion of N276 glycan, and in some cases a glycan shift from position 276 to position 460. Similar signature mutations were found in the envelope of the autologous virus cloned from patient’s plasma. This defines the escape pathways from 179NC75, and shows that they are the same in humans and in HIV-1YU2 infected humanized mice.

Vyšlo v časopise: A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005238
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005238

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