HSV-1 DNA sequence determining intraperitoneal pathogenicity in mice is required for transcription of viral immediate-early genes in macrophages.
The relationship between intraperitoneal (ip) pathogenicity in vivo of herpes simplex virus type 1 (HSV-1) and infection of macrophages (m phi) in vitro was studied. The apathogenic HSV-1 strain HFEM disappeared from the peritoneum of infected mice following ip inoculation, while the pathogenic F strain persisted in the peritoneum and penetrated the mouse nervous system, and eventually the mice died, showing severe neurological signs. When peritoneal m phi were infected in vitro, a direct correlation with pathogenicity in vivo was found with several HSV-1 strains and recombinants. HSV-1 strains (F, KOS, R-M1C1) which were pathogenic for mice by the ip route, induced cytopathic effect (CPE) in m phi in vitro. Strain F transcribed viral immediate-early genes and synthesized viral DNA in m phi that were treated with L-cell conditioned medium (as a source of colony-stimulating factor) prior to infection. Apathogenic HSV-1 strains (HFEM, R-15, R-19) did not cause CPE in m phi. The HFEM strain was already blocked in the transcription of viral alpha genes in the infected m phi, but replicated well in control BSC-1 cells. An intratypic recombinant (R-M1C1), produced by cotransfection of HFEM DNA with a cloned Mlul-Mlul DNA fragment (coordinates 0.7615-0.796) from HSV-1 strain F, that was shown [Becker et al. (1986). Virology 149, 255-259] to have regained partial ip virulence for mice, now transcribed alpha genes, synthesized viral DNA, and induced CPE in m phi. It appears that the viral DNA fragment responsible for ip virulence is involved in tissue-specific recognition of virus by infected m phi, a function necessary for transcription of viral alpha genes.
Ben-Hur
T
T
Department of Molecular Virology, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Rösen-Wolff
A
A
Lamade
W
W
Darai
G
G
Becker
Y
Y
D000818:Animals; D001483:Base Sequence; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics*; D005814:Genes, Viral; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D018139:Simplexvirus / Q000235:genetics* / Q000472:pathogenicity; D014158:Transcription, Genetic; D014774:Virulence; D014779:Virus Replication
D004279:DNA, Viral