Department of Microbiology
Professor
Akio Nomoto, Ph.D.
Associate Professor
Tetsuro Matano, M.D., Ph.D.
Associate
Takeshi Yamada, Ph.D., Seii Ohka, Ph.D.

Organization
Microbial disease has been recognized as the major threat to human health throughout the history. Despite the development of preventive and therapeutic interventions against some pathogenic microbes, infectious disease is still one of the most significant medical problems. On the other hand, microbial organisms have served as a useful model as well for elucidating the molecular mechanisms of a variety of biological events, providing useful insights into life science. Recently, efforts have also been initiated by a number of research groups to utilize animal viruses as a tool for human gene therapy. In order to familiarize students with these issues, importance of microbiology in medical education is increasing more rapidly than ever. To fulfill this requirement, our department, as the only basic microbiology unit in the Faculty, currently assumes a responsibility for teaching bacteriology, mycology, and virology to medical undergraduates.

Teaching Activities
Undergraduate Course, Faculty of Medicine
In a series of lectures (totally 60 hr) and laboratory courses (30 hr), the following subjects are covered.
1) Molecular biology of bacteria, phages, and animal viruses
2) Mechanisms of microbial diseases
3) Laboratory diagnosis of pathogenic microbes
4) Infection control and biosafety
5) Application of microbial organisms for biotechnology
6) Socioeconomic impact of microbial diseases
In addition to the staff of our department, experts from the National Institutes of Infectious Diseases (Dr. Shimada), Dokkyo Medical University (Dr. Masuda), Teikyo University (Dr. Kawana), Faculty of Agriculture (Dr. Onodera), and Institute of Medical Science (Dr. Sasakawa, Dr. Kawaoka, Dr. Iwamoto, and Dr. Saito) contribute to the teaching activities.

Research Activities
1. IRES (internal ribosome entry site)-dependent virus tropism
Honaga, T., Ohka, S., and Nomoto, A.
2. Poliovirus entry into cells and transport
Sakai, M., Ohka, S., and Nomoto, A.
3. Natural function of poliovirus receptor
Oda, T., Ohka, S., and Nomoto, A.
4. Intracellular immunity of neural cells against poliovirus infection
Mitusda, J., Matsuda, N., Hosoda, N., Ohka, S., and Nomoto, A.
5. Translational control - ribosome recycling-
Hosoda, N., Ohka, S., and Nomoto, A.
6. Poliovirus replication and development of poliovirus vector
Yoshino, Y., Fujimaki, T., Ohka, S., and Nomot, A.
7. HCV (hepatitis C virus) genome as an RNA replicon
Yamada, T., Shigenobu, F., Arimoto, K., and Nomoto, A.
8. Molecular basis for HCV pathogenesis
Yamada, T., Murayama, A., and Nomoto, A.
9. Molecular basis for retroviral pathogenesis
Kusuki, K., Sasaki, Y., Kizaki, M., Takeda, A., Igarashi, H., and Matano, T.
10. Virus-specific immune responses
Kawada, M., Kobayashi, M., Tsukamoto, T., Takeda, A., Igarashi, H., and Matano, T.
11. Development of AIDS vaccine
Yamamoto, H., Kato, M., Lun, W.H., Kano, M., Takeda, A., Igarashi, H., and Matano, T.

References
  1. Jia Q, Liang F, Ohka S, Nomoto A, Hashikawa T. Expression of brain-derived neurotrophic factor in the central nervous system of mice using a poliovirus-based vector. J NeuroVirology 8(1): 14-23, 2002.
  2. Nomoto A, Arita I. Eradication of Poliomyelitis. Nature Immunology 3(3): 205-208, 2002.
  3. Feng JY, Ishibashi T, Nomoto A, Masuda M. Isolation and analysis of retroviral integration targets by solo long terminal repeat inverse PCR. J Virol 76(11): 5540-5547, 2002.
  4. Gromeier M, Nomoto A. Determinants of poliovirus pathogenesis. In Molecular Biology of Picornaviruses, Bert L. Semler and Eckard Wimmer eds. ASM Press, pp367-379, 2002.
  5. Iwasaki A, Welker R, Mueller S, Linehan M, Nomoto A, Wimmer E. Immunofluorescence analysis of poliovirus receptor expression in Peyer's patches of humans, primates, and CD155 transgenic mice: implication for poliovirus infection. J Inf Dis 186(5): 585-592, 2002.
  6. Masuda M, Yageta M, Fukuhara H, Kuramochi M, Maruyama T, Nomoto A, Murakami Y. The tumor suppressor protein TSLC1 is involved in cell-cell adhesion. J Biol Chem 277(34): 31014-31019, 2002.
  7. Isoyama T, Kuge S, Nomoto A. The core protein of hepatitis C virus is imported into the nucleus by transport receptor Kap123p but inhibits Kap121p-dependent nuclear import of yeast-AP1-like factor in yeast cells. J Biol Chem 277(42): 39634-39641, 2002.
  8. Horie H, Yoshida H, Matsuura K, Miyazawa M, Wakabayashi K, Nomoto A, Hashizume S. Isolation of vaccine-derived type 1 polioviruses displaying similar properties to virulent wild strain Mahoney from sewage in Japan. J Med Virol 68: 445-451, 2002.
  9. Kano M, Matano T, Kato A, Nakamura H, Takeda A, Suzaki Y, Ami Y, Terao K, Nagai Y. Primary replication of a recombinant Sendai viral vector in macaques. J Gen Virol 83: 1377-1386, 2002.
  10. Kano M, Matano T, Kato A, Shioda T, Nagai Y. Induction of HIV-1-specific neutralizing antibodies in mice vaccinated with a recombinant Sendai virus vector. Jpn J Infect Dis 55: 59-60, 2002.
  11. Matano T. Recent advances in AIDS vaccine preclinical trials: challenges against the chronic disease. Current Topics in Virology 2: 179-185, 2002.
  12. Pelletier I, Ouzilou L, Arita M, Nomoto A, Colbere-Garapin F. Characterization of the poliovirus 147S particles: new insights into poliovirus uncoating. Virology 305(1): 55-65, 2003.
  13. Ida-Hosonuma M, Sasaki Y, Toyoda H, Nomoto A, Gotoh O, Yonekawa H, Koike S. Host range of poliovirus is restricted to simians because of a rapid sequence change of the poliovirus receptor gene during evolution. Arch Virol 148:29-44, 2003.
  14. Yanagiya A, Ohka S, Hashida N, Okamura M, Taya C, Kamoshita N, Iwasaki K, Sasaki Y, Yonekawa H, Nomoto A. Tissue specific replicating capacity of a chimeric poliovirus that carries the internal ribosome entry site of hepatitis C virus in a new mouse model transgenic for human poliovirus receptor. J Virol 77(19): 10479-10487, 2003.
  15. Matano T, Kano M, Takeda A, Nakamura H, Nomura N, Furuta Y, Shioda T, Nagai Y. No significant enhancement of protection by Tat-expressing Sendai viral vector-booster in a macaque AIDS model. AIDS 17: 1392-1394, 2003.
  16. Takeda A, Nakamura H, Matano T. Evaluation of simian immunodeficiency virus-specific immune responses induced by a defective proviral DNA vaccine in macaques. Jpn J Infect Dis 56: 172-173, 2003.
  17. Takeda A, Igarashi H, Nakamura H, Kano M, Iida A, Hirata T, Hasegawa M, Nagai Y, Matano T. Protective efficacy of an AIDS vaccine, a single DNA-prime followed by a single booster with a recombinant replication-defective Sendai virus vector, in a macaque AIDS model. J Virol 77: 9710-9715, 2003.
  18. Fujiyuki T, Takeuchi H, Ono M, Ohka S, Sasaki T, Nomoto A, Kubo T. A novel insect picorna-like virus identified in the brain of aggressive worker honeybees. J Virol 78(3): 1093-1100, 2004.
  19. Nagata N, Iwasaki T, Ami Y, Sato Y, Hatano I, Harashima A, Suzaki Y, Yoshii T, Hashikawa T, Sata T, Horiuchi Y, Koike S, Kurata T, Nomoto A. A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21. Virology, in press.
  20. Ohka S, Matsuda N, Tohyama K, Oda T, Morikawa M, Kuge S, Nomoto A. Receptor (CD155)-dependent endocytosis of poliovirus and retrograde axonal transport of the endosome. J Virol, in press.
  21. Hanaki K, Ohka S, Yamamoto K, Nomoto A, Yoshikura H. Oligo(dA-dT) dependent signal amplification for the detection of proteins in cells. Bio Techniques, in press.
Annual Report of the Graduate School of Medicine and The Faculty of Medicine The University of Tokyo Reports for the Period April 2002 - March 2004