Mutations in the UL53 gene of HSV-1 abolish virus neurovirulence to mice by the intracerebral route of infection.
The cell fusion protein, the product of the UL53 gene, is responsible for intracerebral (IC) pathogenicity of HSV-1. Recombinant HSV-1 R15 is apathogenic to mice by the IC route of inoculation, while intratypic recombinants, in which the UL53 gene in R15 was replaced by an analogous sequence from the pathogenic strain R19, regained IC pathogenicity. The nucleotide sequence of the UL53 gene of HSV-1 strains R15 (apathogenic) and R19 (pathogenic) was determined and compared to that of other pathogenic strains. Four mutations were found which are thought to be responsible for the apathogenic phenotype of HSV-1 strain R15. Northern blot hybridization of RNA extracted from BSC-1 cells infected with several HSV-1 strains indicated that all of the virus strains tested expressed equal amounts of UL53 mRNA in infected cell cultures. Demonstration of the expression of UL53 mRNA in brains of mice infected with HSV-1 strains was made possible by the combined use of a rapid method for mRNA extraction (Oligo dT-linked magnetic beads) and a highly sensitive technique for detection of the existence of the UL53-specific mRNA (cDNA synthesis followed by PCR). It was shown that both pathogenic (KOS and P42) and apathogenic (R15) HSV-1 strains expressed the UL53 gene in brains of IC infected mice.
Moyal
M
M
Department of Molecular Virology, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Berkowitz
C
C
Rösen-Wolff
A
A
Darai
G
G
Becker
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000382:microbiology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005814:Genes, Viral; D006561:Herpes Simplex / Q000209:etiology; D051379:Mice; D008805:Mice, Inbred A; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D018139:Simplexvirus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence / Q000235:genetics
D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; C072448:UL53 protein, Human herpesvirus 1; D014764:Viral Proteins