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 have been studying negative strand RNA viruses including measles virus , human metapneumovirus and influenza virus .
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 is still responsible for 4% of deaths in children younger than age 5 years worldwide. 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.
Our major contributions to measles virus research are the identification of signaling lymphocyte activation molecule (SLAM; also called CD150) as a principal cellular receptor for measles virus (1, 2) and the establishment of reverse genetics for wild-type measles virus (3). 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 (4)
- Development of highly efficient reverse genetics systems for measles virus and measles virus-based novel vectors (5, 6, 7)
- Structural studies of the interaction between measles virus and SLAM
- Identification of an as yet uncharacterized receptor(s) for measles virus
- Measles virus gene expression and assembly (8, 9)
- Molecular mechanisms of measles virus adaptation and attenuation (9, 10)
- Interferon antagonist activities of measles virus (11, 12)
B. HUMAN METAPNEUMOVIRUS
- Establishment of a reverse genetics system
- Virus entry and replication
- Small animal model
C. INFLUENZA VIRUS
- Virus entry and assembly (13)
REFERENCES
1. Tatsuo, H., Ono, N., Tanaka, K., and Yanagi, Y. (2000) SLAM (CDw150) is a cellular receptor for measles virus. Nature . 406. 893-897.
2. Yanagi, Y., Takeda, M., and Ohno, S. (2006) Measles virus: cellular receptors, tropism and pathogenesis (review). J Gen Virol , 87, 2767-2779.
3. Takeda, M, Takeuchi, K., Miyajima, N., Kobune, F., Ami, Y., Nagata, N., Suzaki, Y., Nagai, Y., and Tashiro, M. (2000) Recovery of pathogenic measles virus from cloned cDNA. J Virol, 74, 6643-6647.
4. Ohno, S., Ono, N., Seki, F., Takeda, M., Kura, S., Tsuzuki, T., and Yanagi, Y. Measles virus infection of SLAM (CD150) knock-in mice reproduces tropism and immunosuppression in human infection. J Virol. (in press).
5. Takeda, M., Ohno, S., Seki, F., Hashimoto, K., Miyajima, N., Takeuchi, K., and Yanagi, Y. (2005) Efficient rescue of measles virus from cloned cDNA using SLAM-expressing Chinese hamster ovary cells. Virus Res. 108. 161-165.
6. Nakatsu, Y., Takeda, M., Kidokoro, M., Kohara, M., and Yanagi, Y. (2006) Rescue system for measles virus from cloned cDNA driven by vaccinia virus Lister vaccine strain. J Virol Methods. 137. 152-155.
7. Takeda, M., Nakatsu, Y., Ohno, S., Seki, F., Tahara, M., Hashiguchi, T., and Yanagi, Y. (2006) Generation of measles virus with a segmented RNA genome. J Virol. 80. 4242-4248.
8. Takeda, M., Ohno, S., Seki, F., Nakatsu, Y., Tahara, M., and Yanagi, Y. (2005) Long untranslated regions of the measles virus M and F genes control virus replication and cytopathogenicity. J Virol. 79. 14346-14354.
9. Tahara, M., Takeda, M., and Yanagi, Y. (2005) Contribution of matrix and large protein genes of the measles virus Edmonston strain to growth in cultured cells as revealed by recombinant viruses. J Virol. 79. 15218-15225.
10. Seki, F. Takeda, M., Minagawa, H., and Yanagi, Y. (2006) The recombinant wild-type measles virus containing a single N481Y substitution in its hemagglutinin cannot use a receptor CD46 as efficiently as that having the hemagglutinin of the Edmonston laboratory strain. J Gen Virol. 87. 1643-1648.
11. Ohno, S., Ono, N., Takeda, M., Takeuchi, K., and Yanagi, Y. (2004) Dissection of measles virus V protein in relation to its ability to block interferon-α/β signal transduction. J Gen Virol. 85, 2991-2999.
12. Nakatsu, Y., Takeda, M., Ohno, S., Koga, R., and Yanagi, Y. (2006) Translational inhibition and increased interferon induction in cells infected with a C protein-deficient measles virus. J Virol. 80. 11861-11867.
13. Takeda, M., Leser, G. P., Russell, C. J., and Lamb, R. A. (2003) Influenza virus hemagglutinin concentrates in lipid raft microdomains for efficient viral fusion. Proc Natl Acad Sci U S A, 100, 14610-14617.
