title: Herpes simplex virus serotype and entry receptor availability alter CNS disease in a mouse model of neonatal HSV.
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.
  
  
  CONCLUSIONS
  Dysregulation of inflammatory responses induced by infection may influence the severity of HSV encephalitis.
authors.affiliation: 1] Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois [2] Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Kopp
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Hantamalala R
authors.initials: HR
authors.lastname: Ranaivo
authors.affiliation: 1] Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois [2] Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Wilcox
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Karaba
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wainwright
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: William J
authors.initials: WJ
authors.lastname: Muller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D005838:Genotype; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000075983:Nectins; D010641:Phenotype; D011251:Pregnancy Complications, Infectious / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D065288:Serogroup; D013997:Time Factors; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506029:Tnfrsf14 protein, mouse