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Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates

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
Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 CNRS, U 964 INSERM, Université de Strasbourg, 67081 Strasbourg Cedex, France
Authors to whom correspondence should be addressed.
Present address: Heinrich Pette Institute, Leibniz Institute for Experimental Virology Research Unit Virus Host Interaction, Hamburg 20251, Germany.
Academic Editor: Eric O. Freed
Viruses 2015, 7(5), 2308-2320;
Received: 22 January 2015 / Revised: 23 March 2015 / Accepted: 30 April 2015 / Published: 6 May 2015
(This article belongs to the Section Animal Viruses)
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. View Full-Text
Keywords: Murine Cytomegalovirus; Dicer; encephalitis; imaging Murine Cytomegalovirus; Dicer; encephalitis; imaging
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Ostermann, E.; Macquin, C.; Krezel, W.; Bahram, S.; Georgel, P. Increased Viral Dissemination in the Brain and Lethality in MCMV-Infected, Dicer-Deficient Neonates. Viruses 2015, 7, 2308-2320.

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