MCMV Infection of the Developing CNS: Neuroinvasion and Immune Control (NIH)

MCMV Infection of the Developing CNS: Neuroinvasion and Immune Control



Full title: MCMV Infection of the Developing CNS: Neuroinvasion and Immune Control

Grantor: National Institutes of Health

Grant number: 1R01NS065845-01 (Prime Award)

Grantor's website:

Duration: 2010-2015

Coordinator: William J Britt, University of Alabama at Birmingham, USA

No. of participants: 2

Partner: Stipan Jonjic, Faculty of Medicine University of Rijeka

Coordinator's web site:


Total funding (Sub-award budget): USD 350.000

Brief description:

Congenital human cytomegalovirus (HCMV) infection represents an important cause of neurological damage in children and is the leading cause of non-familial hearing loss in the US. Little is understood about the pathogenesis of this infection because suitable models of central nervous system (CNS) infection are lacking. This group of researchers has developed a murine model of congenital HCMV infection which recapitulates many of the histopathological and neurodevelopmental abnormalities described in congenital HCMV infections, including hearing loss in surviving mice. In contrast to earlier models, newborn mice injected peripherally with murine CMV develop viremia and subsequently, encephalitis. Because newborn mice are neurodevelopmentally and immunologically equivalent to late 2nd trimester human fetuses, this model has also enabled the study of the resolution of this virus infection in a developing animal. Several aspects of the CNS infection in these animals are studied, including mechanisms of neuroinvasion, the contribution of innate immune responses in clearance of the virus from the CNS, and the interplay between innate immunity and adaptive immune responses in clearance of virus from the CNS. Lastly, the role of adaptive immunity in the control of persistent CNS infection in adult mice infected as newborns is studied. The anticipated project result is the identification of the parameters of the pathogenesis of CMV infection in the developing CNS. Furthermore, these findings can be translated directly into more focused studies in humans. Such studies will likely lead to new approaches for prevention and treatment of this important infection.