Role of the herpes simplex virus 1 internal repeat sequences in pathogenicity

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.