Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12202/3683
Title: Murine strain differences in the pathogenesis of mouse adenovirus type 1 hemorrhagic encephalomyelitis
Authors: Guida, Jack Darryl
Keywords: Microbiology.
Genetics.
Veterinary science.
Issue Date: 1997
Publisher: ProQuest Dissertations & Theses
Citation: Source: Dissertation Abstracts International, Volume: 57-06, Section: B, page: 3553.;Advisors: Marshall S. Horwitz.
Abstract: Mouse adenovirus type I (MAV-1) causes a fatal illness consisting of hemorrhagic encephalomyelitis (HEM) and lymphocytic cytolysis in immunocompetent adult C57BL/6 (B6) (50% lethal dose (LD{dollar}\sb{lcub}50{rcub}{dollar}) = 10{dollar}\sp{lcub}3.0{rcub}{dollar} pfu), DBA/2J, and 129/sv, but not in BALB/c (LD{dollar}\sb{lcub}50{rcub}{dollar}, {dollar}\ge{dollar} 10{dollar}\sp{lcub}5.0{rcub}{dollar} pfu) mice. Assessment of viral replication in infected B6 and BALB/c mice, utilizing RNase protection and viral titrations of tissue homogenates showed the greatest amounts of viral message and infectious virus in the brain and spinal cord of B6, but not BALB/c mice. Lower levels of viral message were detected peripherally in both murine strains.;Infection of immunodeficient mice in resistant and susceptible backgrounds demonstrated that B, and/or T cells are important for resistance to disseminated MAV-1 infection but are not required for the prevention or immunopathogenesis of CNS disease. These findings suggest that some other factor in the B6 background is responsible for the MAV-1 sensitivity.;The expression of cytokine mRNA by RNase protection in MAV-1-infected B6 and BALB/c mice showed that interleukin 6 (IL-6) and tumor necrosis factor alpha were elevated in the brains of B6 mice, while IL-1-alpha and beta were upregulated in the BALB/c brain. IL-6 is not required for MAV-1 pathogenesis, however, as IL-6 knockout mice on a susceptible background were not resistant to MAV-1 HEM. Dexamethasone, given at a dose of 6.6 mg/kg one day prior to infection, protected a significant number of infected mice providing further evidence of an immunologic basis for the susceptibility. In contrast to the in vivo data, however, DEX is shown to shorten the MAV-1 replicative cycle in vitro.;The genetic basis of MAV-1 resistance was studied by experimental infection of the BALB/c x B6 (C.B6) F{dollar}\sb1{dollar}, F{dollar}\sb2{dollar} and B6 x C.B6-F{dollar}\sb1{dollar} backcross generations. The F{dollar}\sb1{dollar} animals have an intermediate susceptibility phenotype while the results of the F{dollar}\sb2{dollar} and B{dollar}\sb1{dollar} infections are consistent with inheritance as a single autosomal gene. MAV-1 infection of the CXB recombinant inbred strains 2, 4, 5, 6, and 7 suggests that the gene for MAV-1 resistance is most likely located on mouse chromosome 15 between Tgn and Gdc1.
URI: https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:9634688
https://hdl.handle.net/20.500.12202/3683
Appears in Collections:Albert Einstein College of Medicine: Doctoral Dissertations

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