Herpes Simplex Virus-2 Variation Contributes to Neurovirulence During Neonatal Infection

Cooper K. Hayes, Christopher K. Villota, Fiona B. Mcenany, Stacey Cerón, Sita Awasthi, Moriah L. Szpara, Harvey M. Friedman, David A. Leib, Richard Longnecker, Matthew D. Weitzman, Lisa N. Akhtar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Herpes simplex virus (HSV) infection of the neonatal brain causes severe encephalitis and permanent neurologic deficits. However, infants infected with HSV at the time of birth follow varied clinical courses, with approximately half of infants experiencing only external infection of the skin rather than invasive neurologic disease. Understanding the cause of these divergent outcomes is essential to developing neuroprotective strategies. To directly assess the contribution of viral variation to neurovirulence, independent of human host factors, we evaluated clinical HSV isolates from neonates with different neurologic outcomes in neurologically relevant in vitro and in vivo models. We found that isolates taken from neonates with encephalitis are more neurovirulent in human neuronal culture and mouse models of HSV encephalitis, as compared to isolates collected from neonates with skin-limited disease. These findings suggest that inherent characteristics of the infecting HSV strain contribute to disease outcome following neonatal infection.

Original languageEnglish (US)
Pages (from-to)1499-1509
Number of pages11
JournalJournal of Infectious Diseases
Issue number9
StatePublished - Nov 1 2022


  • encephalitis
  • herpes simplex virus
  • neonate
  • neurovirulence

ASJC Scopus subject areas

  • General Medicine


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