Nevels Lab Profile
Research Focus: Epigenetics of Human Cytomegalovirus Infection
Human Cytomegalovirus (CMV) is a large herpesvirus that latently persists in the majority of people world wide. CMV can cause life-threatening diseases in people with immature or compromised immune systems including unborn and newborn children, transplant recipients, and AIDS patients. In infected cells the viral double-stranded DNA genome is associated with cellular histones in an undefined chromatin-like conformation. We have previously shown that a key transactivator of CMV, the major immediate-early (IE) 1 gene product, is a chromatin-associated protein that facilitates productive viral replication through interaction with and inactivation of nuclear host cell factors, including histone deacetylases (HDACs). Evidence also suggests that HDACs can actively suppress viral replication. We hypothesize that histones and histone-modifying enzymes like HDACs represent components of an intrinsic intranuclear host defense system which has the potential to efficiently block infection at a very early stage by epigenetic silencing of viral gene expression. In this scenario, CMV IE proteins promote viral transcription and replication by counteracting this chromatin-based cellular repression mechanism. The interplay between epigenetic host defense and virulence may be exploited for preventiv or therapeutic antiviral strategies that shift this balance towards the host. We want to extend our standard of knowledge about the dynamic structural and functional changes in viral and cellular chromatin that occur in the course of a CMV infection of human cells. Our work will determine the nucleosomal structure of viral chromatin and the epigenetic signature of CMV-infected cells including posttranslational histone modifications. We are also going to further elucidate the role of the viral IE proteins in chromatin-based control of virus infection, and we will investigate possible implications of epigenetic events in the regulation of the switch between latent and lytic infectious cycles, and species- or cell type-specific viral replication.
Michael Nevels - PIUniversity of Regensburg
Tel: +49 941 944 4640
Institute for Medical Microbiology and Hygiene
Franz-Josef-Strauss-Allee 11, Germany