Inhibition of Wild-Type HIV-1 Virus Production by a Matrix Deficient Gag Mutant

Abstract Previous studies have shown that certain HIV-1 Gag mutants can interfere with the production of infectious HIV-1 when coaxpressed with wild-type virus. In this paper, we studied two mutants of HIV-1 for their ability to interfere with the production of wild-type virus. Both mutants lack the entire matrix domain of gag and either lack [myr(-)MA(-)] or contain [myr(+)MA(-)] an amino-terminal myristate (myr) addition sequence at the beginning of the capsid domain. Previously we have demonstrated that expression of both mutant constructs leads to assembly and release of mutant viruses, although only myr(+)MA(-) particles are released efficiently. Particles produced by both matrix-deficient mutants are noninfectious and poorly incorporate and/or retain viral envelope glycoproteins. In this study, we further show that expression of myr(+)MA(-), but not myr(-)MA(-) interferes with wild-type HIV-1 virus production in transient expression assays. Our data suggest that wild-type and myristylated MA(-) Gag protein interacts at some point during assembly and that Gag myristylation has a greater effect on the assembly pathway than the matrix domain.