title: Cytomegalovirus-induced sensorineural hearing loss with persistent cochlear inflammation in neonatal mice.
abstract: Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL) in children. During murine (M)CMV-induced encephalitis, the immune response is important for both the control of viral dissemination and the clearance of virus from the brain. While the importance of CMV-induced SNHL has been described, the mechanisms surrounding its pathogenesis and the role of inflammatory responses remain unclear. This study presents a neonatal mouse model of profound SNHL in which MCMV preferentially infected both cochlear perilymphatic epithelial cells and spiral ganglion neurons. Interestingly, MCMV infection induced cochlear hair cell death by 21 days post-infection, despite a clear lack of direct infection of hair cells and the complete clearance of the virus from the cochlea by 14 dpi. Flow cytometric, immunohistochemical, and quantitative PCR analysis of MCMV-infected cochlea revealed a robust and chronic inflammatory response, including a prolonged increase in reactive oxygen species production by infiltrating macrophages. These data support a pivotal role for inflammation during MCMV-induced SNHL.
authors.affiliation: Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Schachtele
authors.forename: Manohar B
authors.initials: MB
authors.lastname: Mutnal
authors.forename: Mark R
authors.initials: MR
authors.lastname: Schleiss
authors.forename: James R
authors.initials: JR
authors.lastname: Lokensgard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000032:analysis; D002648:Child; D003001:Cloning, Molecular; D003051:Cochlea / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D003587:Cytomegalovirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology* / Q000821:virology; D004926:Escherichia coli; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D005434:Flow Cytometry; D006319:Hearing Loss, Sensorineural / Q000209:etiology* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000821:virology; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D018146:Muromegalovirus / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D009474:Neurons / Q000473:pathology* / Q000821:virology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D011994:Recombinant Proteins