A point mutation in a herpesvirus polymerase determines neuropathogenicity
Laura B Goodman1, Arianna Loregian, Gillian A Perkins
1Department of Microbiology and Immunology, Cornell University, Ithaca, New York, United States of America.
Plos Pathogens
|November 14, 2007
Summary
A single amino acid change in equid herpesvirus type 1 (EHV-1) DNA polymerase dictates neuropathogenicity. The D752 variant causes neurologic disease in horses, while N752 does not, impacting EHV-1 spread.
Area of Science:
- Veterinary Virology
- Molecular Epidemiology
- Equine Infectious Diseases
Background:
- Equid herpesvirus type 1 (EHV-1) causes significant health issues in horses, including respiratory illness, abortion, and neurological disorders.
- A specific DNA polymerase amino acid variation (N752/D752) in EHV-1 strains correlates with neuropathogenic potential.
Purpose of the Study:
- To investigate if the N752/D752 amino acid variation in EHV-1 DNA polymerase is solely responsible for the virus's neuropathogenic potential.
Main Methods:
- Generation of recombinant EHV-1 viruses with distinct polymerase sequences (N752 and D752).
- Infection of horses to assess neurological signs, viremia, and viral shedding.
- In vitro replication studies in fibroblasts and epithelial cells.
- Analysis of viral sensitivity to aphidicolin.
Main Results:
- The D752 virus induced central nervous system inflammation and ataxia in horses, unlike the N752 mutant.
- Neurologic disease in D752-infected horses was associated with higher viremia levels.
- Both viruses showed similar replication in cell cultures but differed in leukocyte tropism.
- The N752 mutant exhibited increased sensitivity to aphidicolin.
Conclusions:
- A single amino acid substitution in the EHV-1 DNA polymerase is sufficient to determine neuropathogenic potential.
- This variation affects disease severity without significantly altering nasal shedding, crucial for transmission dynamics.
- The predominance of the N752 genotype may indicate a balance between reduced pathogenicity and efficient inter-individual transmission.
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