Human cytomegalovirus (HCMV) infection can cause life-threatening disease in immunodeficient hosts. Experimental infection in mice has revealed that natural resistance to murine cytomegalovirus (MCMV) is genetically determined and mediated by binding of the natural killer (NK) cell activating receptor Ly49H to the pathogen-encoded glycoprotein m157. The study of genetically diverse wild-derived strains revealed natural resistance in the PWK/Pas mouse. However, intracellular staining of NK cells indicated that PWK/Pas mice do not express Ly49H. Moreover, PWK/Pas were also found to be resistant to mutant virus lacking m157. Analysis of backcrosses to a susceptible strain demonstrated that MCMV-resistance is controlled by a major dominant gene effect linked to the Ly49 gene cluster and a modest influence of the major histocompatibility complex (H2). Ly49 cDNAs encoding four novel activating receptors were identified as candidate genes for the resistance phenotype. Our results provide genetic evidence for the existence of alternative NK cell receptors that mediate resistance to viral infection in mice by mechanisms other than recognition of m157. Functionally homologous innate resistance genes may be found in human populations.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.82241 |
| Date | January 2005 |
| Creators | Girard Adam, Sonia |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002198698, proquestno: AAIMR12452, Theses scanned by UMI/ProQuest. |
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