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NLM AIDSLINE

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




 

Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2704-9. Unique Identifier :

Genetic and biochemical analyses of the Gag protein of HIV-1 indicate a crucial role for this protein in several functions related to viral replication, including viral assembly. It has been suggested that Gag may fulfill some of the functions by recruiting host cellular protein(s). In our effort to identify structural and functional homologies between Gag and cellular cytoskeletal and secretory proteins involved in transport, we observed that HIV-1 Gag contains a unique PGQM motif in the capsid region. This motif was initially noted in the regulatory domain of synexin the membrane fusion protein of Xenopus laevis. To evaluate the functional significance of the highly conserved PGQM motif, we introduced alanine (A) in place of individual residues of the PGQM and deleted the motif altogether in a Gag expression plasmid and in an HIV-1 proviral DNA. The proviral DNA containing mutations in the PGQM motif showed altered expression, assembly, and release of viral particles in comparison to parental (NL4-3) DNA. When tested in multiple- and single-round replication assays, the mutant viruses exhibited distinct replication phenotypes; the viruses containing the A for the G and Q residues failed to replicate, whereas A in place of the P and M residues did not inhibit viral replication. Deletion of the tetrapeptide also resulted in the inhibition 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.

JOURNAL ARTICLE Animal Annexin VII/*GENETICS Gene Products, gag/*GENETICS Human HIV-1/*PHYSIOLOGY Mutation Sequence Analysis Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Virus Replication/*GENETICS Xenopus laevis



 




Information in this article was accurate in July 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.