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Role of the herpes simplex virus 1 internal repeat sequences in pathogenicity
1Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Md 20814-4799.
Abstract:
Three independently isolated herpes simplex virus type 1 recombinant viruses containing a deletion of approximately 14 kilobase pairs, representing greater than 95% of the internal repeat DNA sequences, were analyzed for their pathogenicity in mice. The recombinant viruses were found to be avirulent, exhibiting drastically increased LD50 values over wild-type herpes simplex virus 1(F) by intracerebral injection, nonneuroinvasive, unable to spread from the cornea to sensory ganglion, and unable to establish a reactivable latent infection in trigeminal ganglion following either intracerebral inoculation or inoculation of scarified corneas. The potential role of diploid genes in herpes simplex virus pathogenesis in the mouse is discussed.
Insights
Herpes simplex virus type 1 (HSV-1) recombinants lacking internal repeat DNA were avirulent in mice. These HSV-1 mutants could not spread from the cornea or establish latent infections, indicating the importance of these DNA sequences in pathogenesis.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Herpes simplex virus type 1 (HSV-1) is a significant human pathogen.
- HSV-1 pathogenesis involves complex interactions between viral genetic elements and host immune responses.
- Internal repeat DNA sequences in HSV-1 have been implicated in viral replication and latency.
Purpose of the Study:
- To investigate the role of internal repeat DNA sequences in HSV-1 pathogenicity.
- To assess the neuroinvasiveness and latency establishment of HSV-1 recombinants with deleted internal repeats.
- To evaluate the potential role of diploid genes in HSV-1 pathogenesis.
Main Methods:
- Construction of three independent HSV-1 recombinant viruses with deletions in internal repeat DNA sequences (approximately 14 kbp).
- Pathogenicity testing in mice, including intracerebral inoculation and corneal scarification.
- Determination of lethal dose 50 (LD50) values.
- Assessment of neuroinvasion from the cornea to sensory ganglia and latency establishment in the trigeminal ganglion.
Main Results:
- Recombinant HSV-1 viruses with extensive deletions of internal repeat DNA were found to be avirulent in mice.
- These avirulent HSV-1 mutants exhibited significantly increased LD50 values compared to wild-type HSV-1(F).
- The recombinant viruses were nonneuroinvasive, unable to spread from the cornea to sensory ganglia, and failed to establish reactivable latent infections.
Conclusions:
- Internal repeat DNA sequences are critical for HSV-1 pathogenicity, neuroinvasion, and the establishment of latent infections in mice.
- The deletion of these sequences renders HSV-1 avirulent and non-latent.
- These findings highlight the importance of specific viral genetic elements in controlling HSV-1 disease progression and persistence.