ASSEMBLY, PROCESSING, AND INFECTIVITY OF HUMAN-IMMUNODEFICIENCY-VIRUSTYPE-1 GAG MUTANTS

We studied the effects of gag mutations on human immunodeficiency viru s type 1 (HIV-1) assembly, processing, and infectivity by using a repl ication-defective HIV expression system. HIV mutants were screened for infectivity by transduction of a selectable marker and were examined for assembly by monitoring particle release from transfected cells. Ga g protein processing and reverse transcriptase activities of mutant pa rticles were also assayed. Surprisingly, most Gag protein mutants were assembled and processed. The two exceptions to this rule were a myris tylation-minus mutant, and one gag matrix domain mutant which expresse d proteins that were trapped intracellularly. Interestingly, a mutant with a 56-amino-acid deletion within the HIV gag capsid domain still c ould assemble and process virus particles, exhibited a wild-type retro virus particle density, and had wild-type reverse transcriptase activi ty. Indeed, although most HIV-1 gag mutants were noninfectious or poor ly infectious, they produced apparently normal particles which possess ed significant reverse transcriptase activities. These results strongl y support the notion that the HIV-1 Gag proteins are functionally invo lved in postassembly, postprocessing stages of virus infectivity.