RESCUE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MATRIX PROTEIN MUTANTS BY ENVELOPE GLYCOPROTEINS WITH SHORT CYTOPLASMIC DOMAINS

The matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) forms the outer protein shell directly underneath the lipid envelope of the virion. The MA protein has a key role in different aspects of v irus assembly, including the incorporation of the HIV-1 Env protein co mplex, which contains a transmembrane glycoprotein with an unusually l ong cytoplasmic tail. In this study, we compared the abilities of HIV- 1 MA mutants to incorporate Env protein complexes with long and short cytoplasmic tails. While the mutant particles failed to incorporate th e authentic HIV-1 Env protein complex, they retained the ability to ef ficiently and functionally incorporate the amphotropic murine leukemia virus Env protein complex, which has a shore cytoplasmic tail, Moreov er, incorporation of the autologous Env protein complex could be resto red by a second-site mutation that resulted in the truncation of the c ytoplasmic tail of the HIV-1 transmembrane glycoprotein. Remarkably, t he second-site mutation also restored the ability of MA mutants to rep licate in MT-4 cells. These results imply that the long cytoplasmic ta il of the transmembrane glycoprotein is responsible for the exclusion of the HIV-1 Env protein complex from MA mutant particles.