title: Missense mutations in the VP1 gene of simian virus 40 that compensate for defects caused by deletions in the viral agnogene.
abstract: Simian virus 40 mutants lacking sequences in the late leader region are viable but produce smaller plaques than does wild-type virus. Within three passages at low multiplicities of infection, virus stocks of several such mutants accumulated variants that synthesized an altered form of the major virion protein, VP1, having a slightly faster mobility in sodium dodecyl sulfate-polyacrylamide gels than did the wild-type protein. Because these variants overgrew the original virus stocks, we consider them to be second-site revertants. By construction and characterization of a series of recombinants, the second-site mutations were shown to map to at least two different regions of the VP1 gene. Nucleotide sequence analysis indicated that single-amino-acid changes were responsible for the rapid mobility of VP1. When combined in cis with either a wild-type or mutant leader region, these VP1 mutations sped up by 10 to 20 h the time course of accumulation of infectious progeny but not of viral DNA or VP1. LP1, the protein encoded by the agnogene, was shown previously to be necessary for the efficient transport of the virion proteins to the nucleus or for their efficient assembly with viral minichromosomes. The VP1 missense mutations reported here compensate for the lack of LP1 by facilitating this process. On the basis of these findings and findings reported previously by us and others, we hypothesize that LP1 facilitates the formation of infectious particles by inhibiting the polymerization of VP1 molecules until the time they interact with viral minichromosomes; the VP1 mutations reported here compensate for the loss of LP1 by lessening the potential of VP1 for self-polymerization.
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004262:DNA Restriction Enzymes; D004279:DNA, Viral / Q000032:analysis; D005814:Genes, Viral; D009154:Mutation; D010641:Phenotype; D013539:Simian virus 40 / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015678:Viral Structural Proteins
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins; D015678:Viral Structural Proteins; D004262:DNA Restriction Enzymes