title: A NK complex-linked locus restricts the spread of herpes simplex virus type 1 in the brains of C57BL/6 mice.
abstract: The most frequent cause of sporadic viral encephalitis in western countries is Herpes simplex virus (HSV). Despite treatment, mortality rates reach 20-30% while survivors often suffer from significant morbidity. In mice, resistance to lethal Herpes simplex encephalitis (HSE) is multifactorial and influenced by mouse and virus strain as well as route of infection. The ability to restrict viral spread in the brain is one factor contributing to resistance. After infection of the oral mucosa with HSV type 1 (HSV-1), virus spreads throughout the brains of susceptible strains but is restricted in resistant C57BL/6 mice. To further investigate restriction of viral spread in the brain, mendelian analysis was combined with studies of congenic, intra-natural killer complex (intra-NKC) recombinant and antibody-depleted mice. Results from mendelian analysis support the restriction of viral spread as a dominant trait and consistent with a single gene effect. In congenic mice, the locus maps to the NKC on chromosome 6 and is provisionally termed Herpes Resistance Locus 2 (Hrl2). In intra-NKC recombinants, the locus is further mapped to the segment Cd69 through D6Wum34; a different location from previously identified loci (Hrl and Rhs1) also associated with HSV-1 infection. Studies with antibody-depleted mice indicate the effect of this locus is mediated by NK1.1(+) expressing cells. This model increases our knowledge of lethal HSE, which may lead to new treatment options.
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Lorne F
authors.initials: LF
authors.lastname: Kastrukoff
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Allen S
authors.initials: AS
authors.lastname: Lau
authors.affiliation: The Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
authors.forename: Fumio
authors.initials: F
authors.lastname: Takei
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.affiliation: Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia, Australia.|Centre for Ophthalmology and Vision Science, M517, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Scalzo
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001921:Brain / Q000502:physiology* / Q000821:virology; D033481:Chromosomes, Mammalian / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology* / Q000635:transmission; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000502:physiology* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B