DNA sequence of mutations induced in cells by herpes simplex virus type-1.
The shuttle vector plasmid pZ189 was used to find the kinds of mutations that are induced in cells by herpes simplex virus type-1 (HSV-1). A significant increase in mutation frequency was detected as early as 2 hr after infection, and reached a peak of two- to sevenfold over background at 4 hr after infection. Several differences were detected between spontaneous mutants and those induced by HSV-1 when they were analyzed by gel electrophoresis and DNA sequencing. Point mutations accounted for 63% of spontaneous mutants but for only 44% of HSV-1-induced mutants (P less than 0.05). In each case the predominant type of point mutation was the G:C to A:T transition, which comprised 51% of point mutations induced by HSV-1, and 32% of spontaneous point mutations. Deletions of DNA were seen in HSV-1-induced mutants at a frequency of 44%, compared with only 29% in spontaneous mutants. HSV-1-induced deletions were less than half the length of spontaneous deletions, and 3 contained short filler sequences. An increase in size was seen in 13% of HSV-1-induced mutants and was due either to duplication of plasmid DNA, or, in 8 instances, to insertion of sequences derived from cellular DNA. Among spontaneous mutants, only 8% were increased in size and none of them had inserted cellular DNA. The proportion of complex mutants increased as infection by the virus progressed and they accounted for 79% of mutants at 24 hr after infection. The observed mutations have implications for understanding the "hit and run" mechanism of malignant transformation of cells by HSV-1.
Hwang
C B
CB
Department of Microbiology, University of Texas Dental Branch, Houston 77225.
Shillitoe
E J
EJ
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002872:Chromosome Deletion; D004279:DNA, Viral / Q000032:analysis*; D005787:Gene Frequency; D006561:Herpes Simplex / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D018139:Simplexvirus / Q000235:genetics*
D004279:DNA, Viral