Pathogenesis of neonatal herpes simplex 2 disease in a mouse model is dependent on entry receptor expression and route of inoculation

Sarah J. Kopp, Andrew H. Karaba, Laura K. Cohen, Ghazal Banisadr, Richard J Miller, William J Muller*

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Herpes simplex virus (HSV) pathogenesis in mice differs based on availability of the principal entry receptors herpesvirus entry mediator (HVEM) and nectin-1 in a manner dependent upon route of inoculation. After intravaginal or intracranial inoculation of adult mice, nectin-1 is a major mediator of neurologic disease, while the absence of either receptor attenuates disease after ocular infection. We tested the importance of receptor availability and route of infection on disease in mouse models of neonatal HSV. We infected 7-day-old mice lacking neither or one principal HSV receptor or both principal HSV receptors with HSV-2 via a peripheral route (intranasal), via a systemic route (intraperitoneal), or by inoculation directly into the central nervous system (intracranial). Mortality, neurologic disease, and visceral dissemination of virus were significantly attenuated in nectin-1 knockout mice compared with HVEM knockout or wild-type mice after intranasal inoculation. Mice lacking both entry receptors (double-knockout mice) showed no evidence of disease after inoculation by any route. Nectin-1 knockout mice had delayed mortality after intraperitoneal inoculation relative to wild-type and HVEM knockout mice, but virus was able to spread to the brain and viscera in all genotypes except double-knockout mice. Unlike in adult mice, HVEM was sufficient to mediate disease in neonatal mice after direct intracranial inoculation, and the absence of HVEM delayed time to mortality relative to that of wild-type mice. Additionally, in wild-type neonatal mice inoculated intracranially, HSV antigen did not primarily colocalize with NeuNpositive neurons. Our results suggest that differences in receptor expression between adults and newborns may partially explain differences in susceptibility to HSV-2.

Original languageEnglish (US)
Pages (from-to)474-481
Number of pages8
JournalJournal of virology
Volume87
Issue number1
DOIs
StatePublished - Jan 1 2013

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herpes simplex
Herpes Simplex
disease models
Receptors, Tumor Necrosis Factor, Member 14
pathogenesis
animal models
receptors
mice
Simplexvirus
Knockout Mice
Virus Receptors
viruses
Human herpesvirus 2
Human Herpesvirus 2
neonates
Nervous System Diseases
nervous system diseases
Infant, Newborn, Diseases
Mortality
Neonatal herpes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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title = "Pathogenesis of neonatal herpes simplex 2 disease in a mouse model is dependent on entry receptor expression and route of inoculation",
abstract = "Herpes simplex virus (HSV) pathogenesis in mice differs based on availability of the principal entry receptors herpesvirus entry mediator (HVEM) and nectin-1 in a manner dependent upon route of inoculation. After intravaginal or intracranial inoculation of adult mice, nectin-1 is a major mediator of neurologic disease, while the absence of either receptor attenuates disease after ocular infection. We tested the importance of receptor availability and route of infection on disease in mouse models of neonatal HSV. We infected 7-day-old mice lacking neither or one principal HSV receptor or both principal HSV receptors with HSV-2 via a peripheral route (intranasal), via a systemic route (intraperitoneal), or by inoculation directly into the central nervous system (intracranial). Mortality, neurologic disease, and visceral dissemination of virus were significantly attenuated in nectin-1 knockout mice compared with HVEM knockout or wild-type mice after intranasal inoculation. Mice lacking both entry receptors (double-knockout mice) showed no evidence of disease after inoculation by any route. Nectin-1 knockout mice had delayed mortality after intraperitoneal inoculation relative to wild-type and HVEM knockout mice, but virus was able to spread to the brain and viscera in all genotypes except double-knockout mice. Unlike in adult mice, HVEM was sufficient to mediate disease in neonatal mice after direct intracranial inoculation, and the absence of HVEM delayed time to mortality relative to that of wild-type mice. Additionally, in wild-type neonatal mice inoculated intracranially, HSV antigen did not primarily colocalize with NeuNpositive neurons. Our results suggest that differences in receptor expression between adults and newborns may partially explain differences in susceptibility to HSV-2.",
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Pathogenesis of neonatal herpes simplex 2 disease in a mouse model is dependent on entry receptor expression and route of inoculation. / Kopp, Sarah J.; Karaba, Andrew H.; Cohen, Laura K.; Banisadr, Ghazal; Miller, Richard J; Muller, William J.

In: Journal of virology, Vol. 87, No. 1, 01.01.2013, p. 474-481.

Research output: Contribution to journalArticle

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