Laboratory of Virology

Research Outline

The research purpose of our laboratory is to elucidate the elementary processes of vital reactions by making full use of techniques based on molecular biology, biochemistry (enzymology), and cell biology. We promote original drug discovery research based on the results obtained in our studies. Furthermore, we provide technical support for the drug discovery research of IMC by developing experimental systems that can verify the mode of action of novel compounds. We have particularly elucidated the elementary processes underlying the systems of viral and intractable diseases and developed new agents against these diseases.

Theme outline

1. Influenza virus

  • Influenza virus binds to sialic acid on the cell surface (1) and is incorporated into the cell by endocytosis (2). Influenza virus genome RNA is released into the cytoplasm (3) and transported to the cell nucleus. In the nucleus, the viral genome is transcribed to produce viral mRNAs; it is also replicated to produce progeny genome RNAs (4). After transcription and replication, viral mRNAs as well as progeny genome RNAs are transported to the cytoplasm. The viral mRNAs are translated to synthesize viral proteins. Viral proteins and progeny genome RNAs are assembled at the plasma membrane (5), and progeny virions are released from the cell surface (6). Amantadine inhibits membrane fusion during viral genome RNA release into the cytoplasm, and Tamiflu and Relenza inhibit release of progeny virions from the cell surface. However, it is necessary to develop new anti-influenza drugs because viruses resistant to these drugs have been isolated. Thus, we now analyze the molecular mechanisms of transcription and replication of the influenza virus genome as well as the assembly of viral particles and attempt to develop new anti-influenza agents (drugs) and vaccine based on our findings.

Fig.1 Life cycle of influenza virus

2. Retrovirus (HTLV-1, HIV-1)

  • HTLV-1 is a causal agent of human adult T-cell leukemia (ATL), which is resistant to chemical agents and has a poor patient prognosis. Because no preventive methods and effective therapies are available for ATL, there is a great concern about the molecular mechanism and improvement in the treatment. Thus, we attempted to establish a system to identify a biomarker of preclinical diagnosis of ATL and identify a therapeutic chemical compound against ATL.
  • In the past decade, highly active antiretroviral therapy (HAART) has been an effective tool for treating HIV-1 infections, which resulted in a decreasing mortality rate. However, latently infected cells, which persist even in HAART patients without detectable viremia, constitute a major barrier for HIV-1 eradication. Thus, we are particularly interested in understanding how HIV-1 latently infects host cells and are attempting to establish a system to detect HIV-1 latently infected cells in HIV-1 patients receiving HAART.

3. Hepatitis B virus (HBV)

  • Chronic infection of HBV is associated with an elevated risk of developing liver cirrhosis and hepatocellular carcinoma, emphasizing that antiviral drugs are extremely useful for therapeutic treatment to control the infection as well as contributing to a reduction in cirrhosis and cancer development. Although current antiviral drugs, such as interferon alpha (IFN-α), and nucleos(t)ide analogs are effective against HBV infections, these drug classes have certain limitations, such as (1) for IFN-α, a partial efficacy and side effects exist and (2) for nucleos(t)ide analogs, the emergence of drug-resistant virus strains has occurred. Thus, there remains an unmet need for the development of novel anti-HBV drugs. Therefore, we are dedicated to identifying new anti-HBV compounds with emphasis on targeting the virus's unique genome replication cycle.And complete elimination of HBV from the infected cells is rare. The reason is that the cccDNA present in the nuclei is very stable. We are now trying to destroy positively the cccDNA genomes using gene editing techniques aiming development of therapeutic approaches.

Fig.2 Replication cycle of HBV genome

4. Neuromuscular diseases

  • Many neuromuscular diseases are genetic, and most of them have no cure. More, improved treatments are required for them. Therefore, we are attempting to search for new drugs from a natural source and from chemical libraries to treat neuromuscular diseases.