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HSV-1 DNA sequence determining intraperitoneal pathogenicity in mice is required for transcription of viral
T Ben-Hur1, A Rösen-Wolff, W Lamade
1Department of Molecular Virology, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Abstract:
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.
Insights
Herpes simplex virus type 1 (HSV-1) pathogenicity in mice correlates with its ability to infect macrophages (m phi) in vitro. A specific viral DNA fragment influences virulence by enabling m phi recognition and alpha gene transcription.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Herpes simplex virus type 1 (HSV-1) exhibits varying pathogenicity in vivo.
- Macrophages (m phi) play a crucial role in the host immune response to viral infections.
- The interaction between HSV-1 and macrophages is not fully understood in the context of virulence.
Purpose of the Study:
- To investigate the relationship between intraperitoneal (ip) pathogenicity of HSV-1 in mice and its infectivity in macrophages in vitro.
- To identify viral factors contributing to HSV-1 virulence and macrophage interaction.
Main Methods:
- Infection of mice with pathogenic and apathogenic HSV-1 strains via the intraperitoneal route.
- In vitro infection of peritoneal macrophages with different HSV-1 strains and recombinants.
- Analysis of viral gene transcription (immediate-early alpha genes) and DNA synthesis in infected macrophages.
- Characterization of an intratypic recombinant virus with regained virulence.
Main Results:
- Pathogenic HSV-1 strains (F, KOS, R-M1C1) caused cytopathic effect (CPE) in macrophages and persisted in mice, leading to neurological signs and death.
- Apathogenic HSV-1 strains (HFEM, R-15, R-19) did not induce CPE in macrophages; HFEM was blocked in alpha gene transcription.
- An intratypic recombinant (R-M1C1), containing a DNA fragment from strain F, regained partial ip virulence, transcribed alpha genes, synthesized viral DNA, and induced CPE in macrophages.
Conclusions:
- Macrophage infectivity in vitro is directly correlated with HSV-1 pathogenicity in vivo.
- A specific HSV-1 DNA fragment associated with ip virulence mediates tissue-specific recognition by macrophages, essential for viral alpha gene transcription.
- This interaction is a critical factor for HSV-1 virulence and central nervous system penetration.