Objective:
To analyze the diversity of herpes simplex virus type 1 (HSV-1) in newborns and assess the relationship between viral diversity and disease severity.
Approach:
- Sample Collection: Analyzed 30 residual diagnostic samples from 10 newborns at a pediatric hospital from 2009 to 2016.
- Disease Classification: Classified newborns into groups with skin, eye, and mouth disease or severe invasive disease.
- Viral Culture and Sequencing: Performed viral cultures and deep sequencing to assemble consensus genomes from samples.
- Minor Variant Analysis: Quantified minor variants and assessed their frequency in relation to disease severity.
- Neurovirulence Assessment: Conducted intracranial inoculation in mice to evaluate neurovirulence of HSV-1 isolates.
Key Findings:
- HSV-1 diversity was greater between newborns than within the same newborn.
- Minor-variant counts did not significantly differ by disease severity (P > .05).
- Samples that could be cultured had higher viral genome copy numbers (P < .0001).
- Direct patient samples that could not be cultured had more minor variants than culturable samples.
- No significant correlation between human disease diagnosis and murine neurovirulence (P > .05).
Interpretation:
Between-host differences in viral genomes and protein expression were more pronounced than within-host differences, as indicated by the genomic analysis.
Limitations:
- Limited number of clinical source cases.
- Lack of immune measurements for residual samples.
- Potential bias in minor-variant detection due to polymerase chain reaction amplification.
Conclusion:
Further studies are needed to explore genotype-phenotype associations and the implications of viral diversity in neonatal HSV-1 infections.
Sources:
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