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Mechanism of differences in pathogenicity between two variants of a laboratory strain of herpes simplex virus type 1
Abstract:
The mechanisms responsible for the difference in neurovirulence to inbred mice between two variants of the Miyama strain of herpes simplex virus type 1 (HSV-1) were studied. After intraperitoneal (i.p.) inoculation, the +GC (LPV) variant reached the spinal cord and the brain, and caused death. Conversely, the -GCr variant lacked the ability to gain access to the central nervous system (CNS) after the same route of infection and failed to kill susceptible mice. The initial virus growth after i.p. inoculation, as indicated by the number of infective centers (ICs) produced by the peritoneal exudate cells (PECs), was compared between these two variants. The virulent +GC (LPV) strain induced much more ICs than the attenuated -GCr variant. When the attenuated variant was preinoculated i.p. 24 hr before the challenge inoculation with the virulent variant by the same route, the production of ICs by the pathogenic variant was highly inhibited, and growth of this variant did not occur in the CNS. Thus, mice were protected from lethal infection by the virulent variant by preinoculation with the attenuated one. Moreover, the ability of mice to resist i.p. infection by HSV-1 was shown to be age-dependent.
Insights
Two herpes simplex virus type 1 (HSV-1) variants showed different neurovirulence in mice. Pre-inoculation with an attenuated HSV-1 variant protected mice from lethal infection by a virulent variant.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Herpes simplex virus type 1 (HSV-1) causes a range of human diseases.
- Understanding HSV-1 neurovirulence mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the mechanisms underlying differential neurovirulence between two HSV-1 variants.
- To determine the role of initial viral replication and host immune response in HSV-1 neuroinvasion.
Main Methods:
- Intraperitoneal (i.p.) inoculation of inbred mice with two HSV-1 variants (+GC (LPV) and -GCr).
- Comparison of viral replication in peritoneal exudate cells (PECs) and central nervous system (CNS) invasion.
- Assessment of protection conferred by pre-inoculation with the attenuated variant.
Main Results:
- The virulent +GC (LPV) variant accessed the CNS and caused death, while the attenuated -GCr variant did not.
- Virulent +GC (LPV) induced significantly higher infective centers (ICs) in PECs than the -GCr variant.
- Pre-inoculation with the attenuated -GCr variant inhibited virulent +GC (LPV) replication and protected mice from lethal infection.
- HSV-1 infection resistance in mice was found to be age-dependent.
Conclusions:
- Differential neurovirulence of HSV-1 variants is linked to their ability to replicate in peritoneal cells and invade the CNS.
- Attenuated HSV-1 variants can induce protective immunity against virulent strains.
- Age influences the host's ability to resist HSV-1 infection.