HIV-1 Gag shares a signature motif with annexin (Anx7), which is required for virus replication

Genetic and biochemical analyses of the Gag protein of HIV-1 indicate a cru cial role for this protein in several functions related to viral replicatio n, including viral assembly. It has been suggested that Gag may fulfill som e of the functions by recruiting host cellular protein(s). In our effort to identify structural and Functional homologies between Gag and cellular cyo skeletal and secretory proteins involved in transport, se observed that HIV -I Gag contains a unique PGQM motif in the capsid region. This motif was in itially noted in the regulatory domain of synesin the membrane fusion prote in of Xenopus laevis. To evaluate the functional significance of the highly conserved PGQM motif, we introduced alanine (A) in place of individual res idues of the PGQM and deleted the motif altogether in a Gag expression plas mid and in an HIV-1 proviral DNA. The proviral DNA containing mutations in the PGQM motif showed altered expression, assembly, and release of viral pa rticles in comparison to parental (NL4-3) DNA When tested in multiple-and s ingle-round replication assays, the mutant viruses exhibited distinct repli cation phenotypes; the viruses containing the A for the G and Q residues fa iled to replicate, whereas A in place of the P and M residues did not inhib it viral replication. Deletion of the tetrapeptide also resulted in the inh ibition of replication. These results suggest that the PGQM motif may play an important role in the infection process of HIV-1 by facilitating protein -protein interactions between viral and/or viral and cellular proteins.