Efficient incorporation of HLA class II onto human immunodeficiency virus type 1 requires envelope glycoprotein packaging

HLA class II DR is one of the most abundant cell surface proteins incorpora ted onto human immunodeficiency virus type 1 (HIV-1) during budding. The me chanism for HLA class II protein incorporation is not known and may involve a viral protein. To determine whether Env affects HLA class II protein inc orporation, HIV-1 virions, either with or without Env on their surface, wer e produced from HLA class II expressing cells and analyzed by whole-virus i mmunoprecipitation with antisera against HLA class II proteins. HLA class I I proteins were detected on virions only when wild-type Env was incorporate d, while similar experiments showed that HLA class I proteins were incorpor ated independent of Env packaging. Therefore, the packaging of HIV-1 Env pr otein is required for the efficient incorporation of HLA class II but not c lass I proteins into the virion. Analysis of two Env mutants revealed that the presence of a 43-amino-acid sequence between amino acids 708 and 750 in the gp41(TM) cytoplasmic tail was required for efficient incorporation of HLA class II proteins. These data show that HIV-1 actively incorporates HLA class II proteins in a process that, either directly or indirectly, requir es Env.