Variability in the Glycosylation Patterns of gp120 Proteins from Different Human Immunodeficiency Virus Type 1 Isolates Expressed in Different Host Cells.

The mature HIV-1 envelope (Env) glycoprotein is composed of gp120, the exterior subunit, and gp41, the transmembrane subunit assembled as trimer by noncovalent interaction. There is a great body of literature to prove that gp120 binds to CD4 first, then to the coreceptor. Binding experiments and functional assays have demonstrated that CD4 binding induces conformational changes in gp120 that enable or enhance its interaction with a coreceptor. Previous studies provided different glycomic maps for the HIV-1 gp120. Here, we build on previous work to report that the use of LC-MS/MS, in conjunction with hydrophilic interaction liquid chromatography (HILIC) enrichment to glycosylation sites, associated with the assorted neutralizing or binding events of glycosylation targeted antibodies from different clades or strains. In this study, the microheterogeneity of the glycosylation from 4 different clades of gp120s is deeply investigated. Aberrant glycosylation patterns were detected on gp120 that originated from different clades, viral sequences, and host cells. The results of this study may help provide a better understanding of the mechanism of how the glycans participate in the antibody neutralizing process that targets glycosylation sites.