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A sequence in HpaI-P fragment of herpes simplex virus-1 DNA determines intraperitoneal virulence in mice
Abstract:
The virulence of herpes simplex virus-1 (HSV-1) strains by the intraperitoneal (ip) route of injection in mice depends on the presence of an intact sequence in the HpaI DNA fragment P within coordinates 0.762 to 0.787. Deletion of the HpaI-P region (e.g., strain HFEM) abrogates the ability of the virus to infect mice by the ip route without affecting pathogenicity by the intracerebral (ic) route. A recombinant virus (M1C1) derived from DNA of the HSV-1 HFEM strain and the MLUIDNA fragment (coordinates 0.761 to 0.796) spanning the HpaI-P sequence of the pathogenic strain F regained pathogenicity for mice by the ip route.
Insights
Herpes simplex virus-1 (HSV-1) virulence in mice depends on a specific DNA sequence. This region is crucial for intraperitoneal infection but not intracerebral infection.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Herpes simplex virus-1 (HSV-1) causes various infections.
- Understanding HSV-1 virulence factors is crucial for developing antiviral strategies.
- The genetic basis of HSV-1 pathogenicity is complex and not fully elucidated.
Purpose of the Study:
- To identify the specific DNA region responsible for HSV-1 virulence in mice via the intraperitoneal route.
- To investigate the role of the HpaI DNA fragment P in HSV-1 pathogenicity.
- To generate and characterize recombinant HSV-1 strains with altered virulence properties.
Main Methods:
- Comparative analysis of HSV-1 strains with deletions in the HpaI-P region.
- Intraperitoneal (ip) and intracerebral (ic) inoculation of mice with different HSV-1 strains.
- Construction and characterization of recombinant HSV-1 (M1C1) using DNA fragments from different parent strains.
Main Results:
- The HpaI DNA fragment P (coordinates 0.762-0.787) is essential for HSV-1 virulence by the ip route in mice.
- Deletion of the HpaI-P region (strain HFEM) abolished ip pathogenicity but retained ic pathogenicity.
- Reintroduction of the HpaI-P sequence into a non-pathogenic strain (M1C1) restored ip virulence.
Conclusions:
- The HpaI DNA fragment P contains a critical determinant for HSV-1 virulence via the intraperitoneal route in mice.
- This specific DNA sequence plays a distinct role in HSV-1 pathogenesis depending on the route of infection.
- Targeting this viral DNA region could offer a novel approach for controlling HSV-1 infections.