This is a renewal application from an experienced herpes virologist who proposes to study the molecular genetics of cytomegalovirus pathogenesis. During the previous five years of funding, the investigator identified several murine CMV genes which are dispensable for growth in cultured cells but play an important role in the host animal. In particular, the murine CMV protein sgg1 (which is dispensable in cell culture) has been shown to be required for efficient viral replication in the mouse salivary gland, but not in other organs. The first specific aim is to investigate the molecular and cellular basis of viral tropism for epithelial cells. In the second specific aim, the investigator will he will determine how IFNg and TNFa mediate immune clearance in salivary glands of murine CMV infected mice.
The third aim i s to determine the impact of pathogenesis of the C-C chemokine receptor (US28) encoded by human CMV on viral pathogenesis by transfer into the murine CMV genome.
| McCormick, A Louise; Mocarski, Edward S (2015) The immunological underpinnings of vaccinations to prevent cytomegalovirus disease. Cell Mol Immunol 12:170-9 |
| Mocarski, Edward S; Kaiser, William J; Livingston-Rosanoff, Devon et al. (2014) True grit: programmed necrosis in antiviral host defense, inflammation, and immunogenicity. J Immunol 192:2019-26 |
| Kaiser, William J; Sridharan, Haripriya; Huang, Chunzi et al. (2013) Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL. J Biol Chem 288:31268-79 |
| Crosby, Lynsey N; McCormick, A Louise; Mocarski, Edward S (2013) Gene products of the embedded m41/m41.1 locus of murine cytomegalovirus differentially influence replication and pathogenesis. Virology 436:274-83 |
| Kaiser, William J; Upton, Jason W; Mocarski, Edward S (2013) Viral modulation of programmed necrosis. Curr Opin Virol 3:296-306 |
| Upton, Jason W; Kaiser, William J; Mocarski, Edward S (2012) DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe 11:290-7 |
| Tandon, Ritesh; Mocarski, Edward S (2012) Viral and host control of cytomegalovirus maturation. Trends Microbiol 20:392-401 |
| Daley-Bauer, Lisa P; Wynn, Grace M; Mocarski, Edward S (2012) Cytomegalovirus impairs antiviral CD8+ T cell immunity by recruiting inflammatory monocytes. Immunity 37:122-33 |
| Livingston-Rosanoff, Devon; Daley-Bauer, Lisa P; Garcia, AnaPatricia et al. (2012) Antiviral T cell response triggers cytomegalovirus hepatitis in mice. J Virol 86:12879-90 |
| Mocarski, Edward S; Upton, Jason W; Kaiser, William J (2011) Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways. Nat Rev Immunol 12:79-88 |
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