INHIBITION OF WILD-TYPE HIV-1 VIRUS PRODUCTION BY A MATRIX DEFICIENT GAG MUTANT

Previous studies have shown that certain HIV-1 Gag mutants can interfe re with the production of infectious HIV-1 when coexpressed with wild- type virus. In this paper, we studied two mutants of HIV-1 for their a bility to interfere with the production of wild-type virus. Both mutan ts lack the entire matrix domain of gag and either lack [myr(-)MA(-)] or contain [myr(+)MA(-)] an amino-terminal myristate (myr) addition se quence at the beginning of the capsid domain. Previously we have demon strated that expression of both mutant constructs leads to assembly an d release of mutant viruses, although only myr(+)MA(-) particles are r eleased efficiently. Particles produced by both matrix-deficient mutan ts are noninfectious and poorly incorporate and/or retain viral envelo pe glycoproteins. In this study, we further show that expression of my r(+)MA(-), but not myr(-)MA(-) interferes with wild-type HIV-1 virus p roduction in transient expression assays. Our data suggest that wild-t ype and myristylated MA(-) Gag protein interacts at some point during assembly and that Gag myristylation has a greater effect on the assemb ly pathway than the matrix domain. (C) 1995 Academic Press, Inc.