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Journal of Virology, December 2008, p. 12172-12180, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01214-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Passive Immunization Reduces Murine Cytomegalovirus-Induced Brain Pathology in Newborn Mice{triangledown}

Durdica Cekinovic,1 Mijo Golemac,1 Ester Pernjak Pugel,1 Jelena Tomac,1 Luka Cicin-Sain,1,{dagger} Irena Slavuljica,1 Russell Bradford,2 Sonja Misch,3 Thomas H. Winkler,3 Michael Mach,4 William J. Britt,2 and Stipan Jonjic1*

Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Croatia,1 Department of Pediatrics, University of Alabama Birmingham, Birmingham, Alabama,2 Hematopoiesis Unit, Nikolaus Fiebiger Institute for Molecular Medicine, University Erlangen-Nürnberg, Erlangen, Germany,3 Institute for Clinical and Molecular Virology, University Hospital Erlangen, Erlangen, Germany4

Received 12 June 2008/ Accepted 25 September 2008

Human cytomegalovirus (HCMV) is the most frequent cause of congenital viral infections in humans and frequently leads to long-term central nervous system (CNS) abnormalities that include learning disabilities, microcephaly, and hearing loss. The pathogenesis of the CNS infection has not been fully elucidated and may arise as a result of direct damage of CMV-infected neurons or indirectly secondary to inflammatory response to infection. We used a recently established model of mouse CMV (MCMV) infection in newborn mice to analyze the contribution of humoral immunity to virus clearance from the brain. In brains of MCMV-infected newborn mice treated with immune serum, the titer of infectious virus was reduced below detection limit, whereas in the brains of mice receiving control (nonimmune) serum significant amounts of virus were recovered. Moreover, histopathological and immunohistological analyses revealed significantly less CNS inflammation in mice treated with immune serum. Treatment with MCMV-specific monoclonal antibodies also resulted in the reduction of virus titer in the brain. Recipients of control serum or irrelevant antibodies had more viral foci, marked mononuclear cell infiltrates, and prominent glial nodules in their brains than mice treated with immune serum or MCMV-specific antibodies. In conclusion, our data indicate that virus-specific antibodies have a protective role in the development of CNS pathology in MCMV-infected newborn mice, suggesting that antiviral antibodies may be an important component of protective immunological responses during CMV infection of the developing CNS.

* Corresponding author. Mailing address: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, B Branchetta 20, Rijeka 51000, Croatia. Phone: 385 51 651 170. Fax: 385 51 651 176. E-mail: jstipan{at}medri.hr

{triangledown} Published ahead of print on 8 October 2008.

{dagger} Present address: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Beaverton, OR.

Journal of Virology, December 2008, p. 12172-12180, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01214-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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