What is the goal of your research?

Ninety percent of chronic liver inflammation is caused by liver cells infected with one of two types of virus, hepatitis B virus or hepatitis C virus. For many patients, chronic liver inflammation progresses to liver cirrhosis (in which the liver is sclerosed and liver function is reduced), and liver cancer occurs. The number of viral hepatitis patients is as high as approximately 1.5 to 2 million, which is the highest infectious disease in Japan. Therefore, viral hepatitis is considered as the national disease of the 21st century, and its treatments have become a significant challenge.
Many drugs to treat viral hepatitis treatment have been developed over the past several years, and many patients either have been cured, or have succeeded in suppressing the virus for long periods. However, treatment results remain unsatisfactory, and there are still many patients who must continue treatment for their entire lives, or who cannot receive sufficient treatment due to side effects.
In order to develop a therapeutic agent against viral hepatitis, it is necessary to establish virus cell cultures in the laboratory. However, despite both hepatitis B and hepatitis C actively proliferate in human liver cells, it is very difficult to steadily culture these cells in a laboratory. This has been a barrier to the study of virology for many years.

Infection cycle of hepatitis B virus: When HBV infects liver cells, it synthesized a stable virus DNA (covalently closed circular DNA, cccDNA) in the nucleus, and the cell becomes persistently infected. Infection and replication mechanism of hepatitis C virus: When infected, virus protein is translated from the virus genomic RNA, and the virus gene RNA self-duplicates.

Using hepatitis B and hepatitis C viruses isolated from patients, our laboratory has established a cell line that can be cultured stably. Through this, we aim to develop a new, highly effective secure antivirus treatment drug against liver inflammation viruses. 

 

How is your research progressing?

Using hepatitis B and hepatitis C viruses isolated from patients, our laboratory has established a cell line that can be cultured stably. Through this, we aim to develop a new, highly effective secure antivirus treatment drug against liver inflammation viruses.
In our laboratory, we created and cultured HCV replicon cells that make the genome and proteins of hepatitis C virus. HCV replicon is an artificial virus genomic RNA that codes proteins only required for the virus replication in the cell. In the cell with replicon, a state is created as if the real virus continues proliferating at a high rate; however, since infectious virus particles are not secreted from the cell, they can be used safely in a lab.
  Using these replicon cells, we found that reagents such as Cyclosporin A (an immunosuppressant used in organ transplants), Statin (medicine administered to patients with high blood cholesterol), and micro-RNA (small RNA molecules that exists in cells) suppress hepatitis C virus proliferation specifically as an antiviral medication. Based on these findings, a brand new treatment drug has now been developed, and clinical testing is currently being conducted with patients. By combining this with traditional treatment drugs, we succeeded in developing a more effective method of treatment.
  We provided the replicon cells we developed to many research groups inside and outside Japan, and are now working on a wide variety of joint research. We will keep working to develop effective treatment methods for not only the hepatitis C virus but also hepatitis B virus, and to make it a reality for as many patients as possible to benefit from medical care.

 

 

References

(1)    Sakamoto N, Watanabe M: New therapeutic approaches to HCV. J Gastroenterol 2009; 44(7):643-649

(2)  Naoya Sakamoto: Recent Advancements in Hepatitis Virology. Diagnosis and Treatment (Kan-en uirusu gaku kinnen no shinpo. Shindan to chiryou) 2013;101(9): 1283-1286

　　

Hepatitis C virus replicon cell I made. Proliferation same with actual virus occurs.