Abstract
The human immunodeficiency virus type 1 (HIV-1) Matrix (MA) protein, a component of the major structural protein Gag, has been shown to play a role in both the early stages and late stages of the viral life cycle. Functional domains within the MA protein have been identified through numerous mutagenesis studies. In these studies, I investigated the effects of deletions in the C-terminal alpha helix of MA. Removal of amino acids 96 to 120 (MAΔ96-120) resulted in a loss of particle release. Moreover, MAΔ96-120 trans-dominantly inhibited wild type particle release in co-transfection assays. MAΔ96-120 was found to target properly to membranes in membrane floatation assays and to multimerize with wild-type Gag. Electron micrographs revealed the loss of release was due to particle retention at the plasma membrane. Subtilisin treatment failed to release virus, indicating the phenotype was not due to a protaceous factor. The infectivity of the mutants was measured with HIV or vesicular stomatitis virus VSV envelope proteins. All but one (MAΔ107-120) deletion mutant were non-infectious with either envelope. Taken together, these results demonstrate that the C-terminal alpha helix of MA, specifically amino acids 96 to 120, is critical for both virus release and the early steps of HIV infection.