title: N myristoylation of the spleen necrosis virus matrix protein is required for correct association of the Gag polyprotein with intracellular membranes and for particle formation.
abstract: To determine whether myristoylation is required for spleen necrosis virus replication, we constructed a substitution mutation in the gag gene that alters the putative myristate acceptor glycine residue. This single amino acid change was lethal for virus replication, resulted in aberrant proteolytic processing, and interrupted virion assembly and the release of virus from cells. Immunofluorescence analysis indicated that the amount of Gag polyprotein at the cell periphery and in Golgi-associated vesicles is severely reduced in the myristoylation mutant, indicating that correct intracellular targeting is affected by a lack of myristoylation. Coexpression of wild-type Gag polyprotein did not complement and rescue the replication-defective phenotype of the myristoylation mutant. Thus, it appears that the nonmyristoylated polyproteins are incapable of interacting with their myristoylated counterparts to form biologically active particles.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison 53706.
authors.forename: T A
authors.initials: TA
authors.lastname: Weaver
authors.forename: A T
authors.initials: AT
authors.lastname: Panganiban
mesh_terms: D000818:Animals; D002460:Cell Line; D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015750:Genes, gag; D007425:Intracellular Membranes / Q000378:metabolism*; D009154:Mutation; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D003062:Codon; D004279:DNA, Viral; D015683:Gene Products, gag; D009227:Myristic Acids; D014763:Viral Matrix Proteins; D019814:Myristic Acid