Signal peptide of HIV envelope protein impacts glycosylation and antigenicity of gp120

Significance Significant heterogeneity exists in the structure and antigenicity of HIV-1 envelope protein (Env) gp120 due, in part, to various posttranslational modifications. Using glycan and antigenic analysis, we show that the signal peptide (SP) of HIV Env can impact the glycan profile of gp120, which in turn impacts antigenicity of the mature protein. Thus, although the SP is not present in the mature gp120 protein, it is likely subject to immune pressure. Moreover, to the extent that glycan content impacts transmission fitness, variation in the SP may influence transmission. These observations potentially help us better understand both the early events in HIV transmission as well as the mechanisms whereby HIV evades humoral immune responses, providing additional information for HIV vaccine design.