Neonatal HSV-1 diversity greater between patients than within patients

Deep sequencing found no significant association between minor-variant burden and disease severity, although several newborns had unusually high within-host viral diversity.

By
Kathryn Wighton
August 12, 2026
5 min

MDSpire News

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.