PLEIOTROPIC MUTATIONS IN THE HIV-1 MATRIX PROTEIN THAT AFFECT DIVERSESTEPS IN REPLICATION

The matrix domain of the Gag precursor protein, and the mature matrix protein, which is derived from processing of the Gag precursor, functi ons in several steps of the human immunodeficiency virus type-1 (HIV-I ) life cycle. We made numerous mutations throughout the matrix protein and identified three mutants in the N-terminal portion of the matrix that drastically diminish the ability of the virus to replicate. Each of these replication-defective mutants was unable to acquire efficient ly the envelope glycoprotein of HIV-1. To determine whether these same mutations affect other steps in viral replication we pseudotyped muta nt particles with the envelope glycoprotein from an amphotropic murine leukemia virus. Each of these mutants was also hampered in other step s in virus replication. Two mutants were defective in entry or uncoati ng, and the third was hampered in a step following reverse transcripti on. Since viral replication was analyzed under conditions in which the nuclear localization function of the matrix protein is not required, the matrix protein may be required for an additional replication step following reverse transcription. (C) 1997 Academic Press.