Our main research interest is to understand cellular and molecular mechanisms of viral infections and use the knowledge to devise the strategies for the treatment of viral diseases. We are currently studying measles virus, a negative strand RNA virus, and gammaherpesviruses, DNA viruses of the herpesvirus family.
A. MEASLES VIRUS
Measles virus, a member of the paramyxovirus family, causes a common acute infectious disease characterized by fever, cough, conjunctivitis and a generalized maculopapular rash. Despite the availability of effective live vaccines, measles remains a major cause of childhood morbidity and mortality. After an incubation period of 10-14 days, clinical symptoms develop, accompanied with immunosuppression often leading to secondary bacterial infections. Measles virus also causes various types of neurological diseases; postinfectious encephalitis, measles inclusion body encephalitis, and subacute sclerosing panencephalitis. Although numerous studies have been performed, many aspects of measles pathogenesis still remain to be understood.
We have identified signaling lymphocyte activation molecule (SLAM; also called CD150) as a principal cellular receptor for measles virus and developed reverse genetics for measles virus. Based on these studies, we are currently conducting the following projects.
- Study of measles pathogenesis using SLAM knock-in mice as a small animal model
- Structural study of measles virus entry and membrane fusion
- Measles virus entry of neuronal cells
- Identification of an as yet uncharacterized receptor(s) for measles virus
- Measles virus gene expression and assembly
- Host factors required for measles virus replication
- Interferon antagonist activities of measles virus
Murine gammaherpesvirus 68 (MHV68) is a member of the subfamily Gammaherpesvirinae and a pathogen of mice causing infectious mononucleosis (IM)-like symptoms. After the acute infection, MHV68 establishes a life-long persistence in mice, mainly in B cells, dendritic cells, macrophages, and so on. Herpesviruses encode around one hundred genes. Most of them are conserved among all herpesviruses, but some genes are specific for a particular virus or a herpesvirus sub-family. By using BAC system which allows us to introduce various mutations into MHV68 genome, we are characterizing some of herpesvirus genes.
MHV68 causes an IM-like disease in experimental mice, and other diseases such as aortitis and lymphoproliferative disease in immune suppressed mice. These diseases are also caused in humans by human gammaherpesviruses like Epsetin-Barr virus and Kaposi’s sarcoma associated virus. Thus, these MHV68 infected mice can be used as human disease models.