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Our laboratory has focused its efforts on important aspects of the biology of herpesviruses; virus assembly and the pathogenesis of human cytomegalovirus (CMV) infections. We have developed in-vitro systems that permit the identification and characterization of critical host cells:viral protein interactions that take place during virus assembly. Using BAC derived infectious clones, we have utilized virus genetics to understand the role of different viral proteins in the assembly of an infectious particle. Our results indicate that interactions between viral tegument and envelope proteins are essential for infectious particle assembly and that inhibition of these interactions can limit envelopment and therefore, virus assembly. In addition, we have further defined sites of cytoplasmic virus assembly and virus-induced changes in the host secretory and endocytic pathways that facilitate virus assembly, in particular envelopment. A second major focus of our laboratory is the development of a small animal model of CNS disease associated with cytomegalovirus infections. We have exploited a finding that newborn mice infected with murine CMV develop CNS infection that leads to maldevelopment of the CNS, including abnormalities in cellular migration in the CNS and functional impairment such as hearing loss. Using this system we have shown that host innate immune responses and resulting inflammation play a major role in the pathogenesis of virus-induced disease in the developing nervous system. .
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Virusesno. 7 (2023): 1500-1500
Natureno. 7961 (2023): 574-580
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SCIENCE TRANSLATIONAL MEDICINEno. 706 (2023): eadh9917-eadh9917
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