Herpes simplex virus serotype and entry receptor availability alter CNS disease in a mouse model of neonatal HSV

Sarah J. Kopp, Hantamalala R. Ranaivo, Douglas R. Wilcox, Andrew H. Karaba, Mark Wainwright, William J Muller*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background:Outcomes of neonates with herpes simplex virus (HSV) encephalitis are worse after infection with HSV-2 when compared with HSV-1. The proteins herpes virus entry mediator (HVEM) and nectin-1 mediate HSV entry into susceptible cells. Prior studies have shown receptor-dependent differences in pathogenesis that depend on route of inoculation and host developmental age.

Methods:We investigated serotype-related differences in HSV disease and their relationship to entry receptor availability in a mouse model of encephalitis.

Results:Mortality was attenuated in 7-d-old, wild-type (WT) mice inoculated with HSV-1(F) when compared with HSV-2(333). No serotype-specific differences were seen after inoculation of adult mice. HSV-1 pathogenesis was also attenuated relative to HSV-2 in newborn but not adult mice lacking HVEM or nectin-1. HSV-2 requires nectin-1 for encephalitis in adult but not newborn mice; in contrast, nectin-1 was important for HSV-1 pathogenesis in both age groups. Early viral replication was independent of age, viral serotype, or mouse genotype, suggesting host responses influence outcomes. In this regard, significantly greater amounts of inflammatory mediators were detected in brain homogenates from WT newborns 2 d after infection compared with adults and receptor-knockout newborns.

Conclusion:Dysregulation of inflammatory responses induced by infection may influence the severity of HSV encephalitis.

Original languageEnglish (US)
Pages (from-to)528-534
Number of pages7
JournalPediatric Research
Volume76
Issue number6
DOIs
StatePublished - Jan 1 2014

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Virus Internalization
Central Nervous System Diseases
Simplexvirus
Human Herpesvirus 2
Human Herpesvirus 1
Newborn Infant
Herpes Simplex Encephalitis
Encephalitis
Infection
Virus Diseases
Neonatal herpes
Serogroup
Age Groups
Genotype
Mortality
nectins
Brain
Proteins

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

Cite this

Kopp, Sarah J. ; Ranaivo, Hantamalala R. ; Wilcox, Douglas R. ; Karaba, Andrew H. ; Wainwright, Mark ; Muller, William J. / Herpes simplex virus serotype and entry receptor availability alter CNS disease in a mouse model of neonatal HSV. In: Pediatric Research. 2014 ; Vol. 76, No. 6. pp. 528-534.
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Herpes simplex virus serotype and entry receptor availability alter CNS disease in a mouse model of neonatal HSV. / Kopp, Sarah J.; Ranaivo, Hantamalala R.; Wilcox, Douglas R.; Karaba, Andrew H.; Wainwright, Mark; Muller, William J.

In: Pediatric Research, Vol. 76, No. 6, 01.01.2014, p. 528-534.

Research output: Contribution to journalArticle

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AB - Background:Outcomes of neonates with herpes simplex virus (HSV) encephalitis are worse after infection with HSV-2 when compared with HSV-1. The proteins herpes virus entry mediator (HVEM) and nectin-1 mediate HSV entry into susceptible cells. Prior studies have shown receptor-dependent differences in pathogenesis that depend on route of inoculation and host developmental age.Methods:We investigated serotype-related differences in HSV disease and their relationship to entry receptor availability in a mouse model of encephalitis.Results:Mortality was attenuated in 7-d-old, wild-type (WT) mice inoculated with HSV-1(F) when compared with HSV-2(333). No serotype-specific differences were seen after inoculation of adult mice. HSV-1 pathogenesis was also attenuated relative to HSV-2 in newborn but not adult mice lacking HVEM or nectin-1. HSV-2 requires nectin-1 for encephalitis in adult but not newborn mice; in contrast, nectin-1 was important for HSV-1 pathogenesis in both age groups. Early viral replication was independent of age, viral serotype, or mouse genotype, suggesting host responses influence outcomes. In this regard, significantly greater amounts of inflammatory mediators were detected in brain homogenates from WT newborns 2 d after infection compared with adults and receptor-knockout newborns.Conclusion:Dysregulation of inflammatory responses induced by infection may influence the severity of HSV encephalitis.

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