title: p53 status does not determine outcome of E1B 55-kilodalton mutant adenovirus lytic infection.
abstract: The ability of the adenovirus type 5 E1B 55-kDa mutants dl1520 and dl338 to replicate efficiently and independently of the cell cycle, to synthesis viral DNA, and to lyse infected cells did not correlate with the status of p53 in seven cell lines examined. Rather, cell cycle-independent replication and virus-induced cell killing correlated with permissivity to viral replication. This correlation extended to S-phase HeLa cells, which were more susceptible to virus-induced cell killing by the E1B 55-kDa mutant virus than HeLa cells infected during G1. Wild-type p53 had only a modest effect on E1B mutant virus yields in H1299 cells expressing a temperature-sensitive p53 allele. The defect in E1B 55-kDa mutant virus replication resulting from reduced temperature was as much as 10-fold greater than the defect due to p53 function. At 39 degreesC, the E1B 55-kDa mutant viruses produced wild-type yields of virus and replicated independently of the cell cycle. In addition, the E1B 55-kDa mutant viruses directed the synthesis of late viral proteins to levels equivalent to the wild-type virus level at 39 degreesC. We have previously shown that the defect in mutant virus replication can also be overcome by infecting HeLa cells during S phase. Taken together, these results indicate that the capacity of the E1B 55-kDa mutant virus to replicate independently of the cell cycle does not correlate with the status of p53 but is determined by yet unidentified mechanisms. The cold-sensitive nature of the defect of the E1B 55-kDa mutant virus in both late gene expression and cell cycle-independent replication leads us to speculate that these functions of the E1B 55-kDa protein may be linked.
authors.affiliation: Molecular Genetics Program and Department of Microbiology and Immunology, Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
authors.forename: F D
authors.initials: FD
authors.lastname: Goodrum
authors.forename: D A
authors.initials: DA
authors.lastname: Ornelles
mesh_terms: D017501:Adenovirus E1B Proteins / Q000235:genetics* / Q000502:physiology; D000260:Adenoviruses, Human / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D002453:Cell Cycle; D016923:Cell Death; D002460:Cell Line; D004279:DNA, Viral / Q000096:biosynthesis; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D010641:Phenotype; D013696:Temperature; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D017501:Adenovirus E1B Proteins; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53