The role of N-glycosylation sites on the CXCR4 receptor for CXCL-12 binding and signaling and X4 HIV-1 viral infectivity.

The chemokine receptor CXCR4 functions as one of the HIV-1 coreceptors and can be considered as an attractive target for the development of novel anti-HIV drugs. Here, we investigated the effect of its two known N-glycosylation sites g1 (NYT) and g2 (NVS) on the antiviral potential of several classes of entry inhibitors. The lack of g1 clearly affected the binding of the amino-terminal directed 2B11 mAb, but not the 12G5 mAb. No dramatic effects on CXCL-12 binding and CXCL-12-induced intracellular calcium responses were observed. Importantly, the anti-HIV-1 activity and antagonistic activity of the prototype compound of CXCR4 inhibitors, AMD3100, were not affected by the presence or absence of the CXCR4 N-glycans. Since CXCR4 N-glycans play a less important role in viral entry compared to the N-glycans on the HIV envelope, cells expressing CXCR4 N-glycosylation mutants might be no relevant alternative to allow HIV-1 escape from antivirals.