Infection with Human Cytomegalovirus (HCMV), a ubiquitous pathogen in the general population, causes little to no symptoms in healthy individuals. However, the virus can cause severe morbidity and mortality within the immunosupressed and immunocompromised populations. HCMV is a very large (240kB) herpesvirus that encodes up to 200 ORFs which are expressed in a very regulated transcriptional cascade. HCMV, as all herpesviruses, maintains the ability to enter into latency where viral transcription is silenced and the virus remains in a quiescent state while retaining the ability to reactivate as environmental conditions within a host change. Understanding the progression of pathogenesis induced by HCMV is the focus of the laboratory, specifically investigating different factors that regulate the lifecycle of the virus, and how these factors may regulate the maintenance of latency.
My laboratory has identified small RNA transcripts (microRNAs), encoded by both the human genome and the viral genome, that target proteins essential for efficient viral replication. Additionally, we have identified several cellular proteins which are targets for viral encoded microRNAs including factors involved in inducing apoptosis. Current research involves studying the importance of these microRNA induced changes within the cellular environment in relation to the virus lifecycle.
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O’Connor CM and Murphy EA. A myeloid progenitor cell line capable of supporting human cytomegalovirus latency and reactivation resulting in infectious progeny. J Virol 2012, 86:9854-65.
Lee SH, et al. BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection. Proc Natl Acad Sci USA. 2012 109:9575-80.
Murphy E, et al. Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency. Proc Natl Acad Sci USA 2008;105:5453-8.
Wang D, et al. Human cytomegalovirus uses two distinct pathways to enter retinal pigmented epithelial cells. Proc Natl Acad Sci USA 2007;104:20037-42.
Tang Q, Murphy EA, Maul GG. Experimental confirmation of global murine cytomegalovirus open reading frames by transcriptional detection and partial characterization of newly described gene products. J Virol 2006;80:6873-82.
Murphy E, et al. Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc Natl Acad Sci USA 2003;100:14976-81.