Matsuura Lab/Division of Infectious Disease  Department of Molecular Virology

Viruses “know” cells better than human beings and have evolved to replicate in living cells. We are working to understand the molecular mechanisms underlying the interplay between viruses and host cells through research on hepatitis viruses, flaviviruses, and insect viruses.

Molecular biology of hepatitis viruses

Hepatitis C virus (HCV) infects over 170 million individuals worldwide and is one of the most common etiologic agents of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma (HCC). Although novel innovative anti-HCV drugs that act directly on viral proteins have achieved a sustained virological response in hepatitis C patients, drug-resistant viruses emerge easily. Therefore, host factors necessary for HCV replication are ideal targets for the development of new therapeutics for chronic hepatitis C; such drugs will lessen the possibility of drug-resistant breakthrough viruses emerging because the frequency of mutation is much lower than that in the viral genome.
Upon infection with HCV, viral RNA is directly translated into viral proteins. Viral RNA replicates in the cytoplasm using various host factors and organelles. Viruses replicate in living cells, and some of them, including HCV, are pathogenic to the host. We are focusing on trying to understand the molecular mechanisms underlying the interaction between the virus and host by identifying the host factors involved in the propagation and pathogenicity of HCV. We have shown that the HCV core protein participates not only in the assembly of viral particles but also in the development of liver steatosis and HCC. We have also shown that host proteins, including molecular chaperones and apolipoproteins, participate in viral replication and in the formation of infectious particles.
Novel therapeutic agents targeting the host factors crucial for propagation and pathogenesis of HCV could be available if we can elucidate the molecular mechanisms underlying infection and replication of HCV. We are also working on hepatitis B virus and Japanese encephalitis virus, also members of the Flaviviridae.

Development of baculoviral vectors

Development of viral vectors capable of safely transducing foreign genes into target cells is essential for future gene therapy. We are working on developing the insect baculovirus, Autographa californica nucleopolyhedro virus, as a versatile viral vector for gene delivery. Baculovirus is capable of entering a variety of mammalian cells and facilitates expression of foreign genes under the control of mammalian promoters; however, the viral genome does not replicate. We are working on developing viral vectors that have the advantages and characteristics of baculovirus.

Staff

  • Prof.: Yoshiharu Matsuura
  • Prof.: Tokiko Watanabe
  • Asst. Prof.: Chikako Ono
  • Asst. Prof.: Itsuki Anzai
  • Asst. Prof.: Shintaro Shichinohe
  • Postdoc.: Rigel Suzuki
  • Postdoc.: Kousuke Takada
  • Postdoc: Shiho Torii

Website

Publications

  • (1) Infection with flaviviruses requires BCLXL for cell survival. Suzuki T., et al., PLoS Pathog. (2018) 14(9):e1007299.
    (2) Characterization of SPP inhibitors suppressing propagation of HCV and protozoa. Hirano J etal. Proc Natl Acad Sci U S A. 2017 Dec 12;114 (50):E10782-E10791.
    (3) Host-derived apolipoproteins play comparable roles with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae. Fukuhara T et al., PLoS Pathog. 2017 Jun 23;13(6):e1006475.
    (4) Characterization of miR-122-independent propagation of HCV. Ono C, et al. PLoS Pathog. 2017 May 11;13(5):e1006374.
    (5) TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis. Aizawa S. & Okamoto T., et al. Nat. Commun. (2016), doi: 10.1038/ncomms11379.
    (6) Lipoprotein receptors redundantly participate in entry of hepatitis C virus Yamamoto S. & Fukuhara T.,et al. PLoS Pathog. (2016), doi: 10.1371/journal. ppat.1005610.