SUBSTITUTION MUTATIONS AFFECTING A SMALL REGION OF THE MOLONEY MURINELEUKEMIA-VIRUS MA GAG PROTEIN BLOCK ASSEMBLY AND RELEASE OF VIRION PARTICLES

A series of substitution mutations affecting the Moloney murine leukem ia virus MA protein were introduced into a cloned proviral DNA, and th e mutant DNAs were tested for their biological activity in NIH/3T3 cel ls and COS cells. Many of the mutant viruses were viable and replicate d with kinetics indistinguishable from the wild type. Seven mutants wi th alterations in a small region (residues 7-14 from the amino terminu s) were replication-defective. These mutants were blocked in assembly and release of the virion particles in NIH/3T3 cells and were defectiv e in both gag and gag-pol gene function. The results suggest that this very small region near the amino terminus of both proteins is require d for their membrane targeting or self-association. Three of the defec tive mutant DNAs were able to induce virion particle formation when pr esent at high copy number in COS cells. (C) 1994 Academic Press, Inc.