title: Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates.
abstract: Among Herpesviruses, Human Cytomegalovirus (HCMV or HHV-5) represents a major threat during congenital or neonatal infections, which may lead to encephalitis with serious neurological consequences. However, as opposed to other less prevalent pathogens, the mechanisms and genetic susceptibility factors for CMV encephalitis are poorly understood. This lack of information considerably reduces the prognostic and/or therapeutic possibilities. To easily monitor the effects of genetic defects on brain dissemination following CMV infection we used a recently developed in vivo mouse model based on the neonatal inoculation of a MCMV genetically engineered to express Luciferase. Here, we further validate this protocol for live imaging, and demonstrate increased lethality associated with viral infection and encephalitis in mutant mice lacking Dicer activity. Our data indicate that miRNAs are important players in the control of MCMV pathogenesis and suggest that miRNA-based endothelial functions and integrity are crucial for CMV encephalitis.
authors.affiliation: Immunorhumatologie Moléculaire, INSERM UMR S_1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg. 1, Place de l'Hôpital, 67085 Strasbourg Cedex, France. eleonore.ostermann@hpi.uni-hamburg.de.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Ostermann
authors.affiliation: Immunorhumatologie Moléculaire, INSERM UMR S_1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg. 1, Place de l'Hôpital, 67085 Strasbourg Cedex, France. macquin@unistra.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Macquin
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 CNRS, U 964 INSERM, Université de Strasbourg, 67081 Strasbourg Cedex, France. krezel@igbmc.fr.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Krezel
authors.affiliation: Immunorhumatologie Moléculaire, INSERM UMR S_1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg. 1, Place de l'Hôpital, 67085 Strasbourg Cedex, France. siamak@unistra.fr.
authors.forename: Seiamak
authors.initials: S
authors.lastname: Bahram
authors.affiliation: Immunorhumatologie Moléculaire, INSERM UMR S_1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg. 1, Place de l'Hôpital, 67085 Strasbourg Cedex, France. pgeorgel@unistra.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Georgel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology* / Q000821:virology*; D003586:Cytomegalovirus Infections / Q000473:pathology* / Q000821:virology*; D053487:DEAD-box RNA Helicases / Q000172:deficiency*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000473:pathology / Q000821:virology; D005260:Female; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000502:physiology*; D043244:Ribonuclease III / Q000172:deficiency*; D016019:Survival Analysis; D051598:Whole Body Imaging
chemical_list: C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases