Glycosylation of the HIV-1 Env V1V2 loop to form a native-like structure may not be essential with a nanoparticle vaccine

Karch, Christopher P; Matyas, Gary R; Burkhard, Peter; Beck, Zoltan

The only surface protein of human immunodeficiency virus-1 (HIV-1) is the Env fusion protein. Env is heavily glycosylated, with glycans composing up to half of its mass [19] . During maturation of Env, the full-length gp160 is cleaved by a protease into gp41 and gp120, which remain associated forming Env heterodimers. Three heterodimers form a trimeric spike, and approximately 14 spikes decorate the surface of the virus [20, 21] . The majority, about 62-79% of the gp120 glycans present on virus, are underprocessed N-linked high mannose, because the high density of the glycosylation sites can prevent the further processing steps of the glycans by the enzymes in the Golgi apparatus [22] . Changes in the glycosylation pattern of gp120 can alter the receptor binding and infection by the virus, as well as the susceptibility to antibodies [23, 24] . In addition, the high mutation rate of HIV-1 results in an inconsistent level of glycosylation. For example, transmitter/founder viruses generally have a lower number of N-linked glycosylation sites than chronic viruses and appear to be more infectious [25] .