Cerebral Epstein-Barr Virus (EBV) infection: From human disease to an animal model

Objectives: Whereas the neurotropism of EBV is well known, many clinical and therapeutical aspects of cerebral EBV infection are uncertain. An animal model of human cerebral EBV infection is not available.

Material and Methods: Clinical data of patients with neurological EBV-related complications are compared with a newly developed animal model of cerebral EBV-infection.

Results: Performing detailed serological and PCR studies, we found EBV infections in 20 out of 159 consecutive children with inflammatory neurological diseases. This included EBV reactivations in 11 cases. The patients showed typical (encephalitis, headaches, neuritis, ataxia) and unusual presentations (temporal lobe encephalitis (TLE), hydrocephalus). Immunosuppressive and antiviral therapy performed in selected cases was ineffective. To study cerebral gamma-herpesvirus infections we established a new animal model. It is based on nasal infection of newborn BALB/c wild type mice with MHV-68, a gamma-herpesvirus closely related to EBV. 50% of the mice developed cerebral lesions strikingly similar to human cerebral EBV infection. Even hydrocephali and TLE were observed.

Conclusions: This new animal model represents a promising tool to study immunological, virological and therapeutical aspects of neurological diseases caused by gamma-herpesviruses. It confirms the important role of herpesviruses, in general, for inflammatory temporal lobe diseases.