Multi-phenotype analysis for enhanced classification of 11 herpes simplex virus 1 strains

Area of Science:

• Virology
• Genetics
• Infectious Diseases

Background:

• Herpes simplex virus 1 (HSV1) causes diverse clinical outcomes, from mild oral lesions to severe disease.
• Understanding the factors driving HSV1 phenotypic variation, including disease severity and reactivation rates, is crucial for managing infections.

Purpose of the Study:

• To characterize genomic and in vitro plaque phenotypes of 11 HSV1 strains.
• To correlate these characteristics with previously quantified disease phenotypes in a murine model.
• To identify distinct HSV1 strain clusters based on multi-parameter phenotyping.

Main Methods:

• Genomic analysis of 11 HSV1 isolates.
• In vitro plaque phenotype analysis.
• Comparison with existing murine model disease quantitation data.
• Comparative genomics and network graph analysis.

Main Results:

• Integration of genomic, plaque, and animal model data enabled clustering of HSV1 strains into four distinct groups.
• Group 1 strains exhibited syncytial plaques and attenuated murine disease.
• Groups 2, 3, and 4 showed varying plaque sizes, genetic clustering, and disease severities, with comparative genomics suggesting a link between genetic variation and virulence.

Conclusions:

• Combinatorial multi-parameter phenotyping is essential for distinguishing HSV1 strain variations.
• Genetic variations within the HSV1 population appear to correlate with attenuated versus virulent phenotypes.
• This study provides insights into the genetic basis of HSV1 virulence.