Institute of Biomedical Research and InnovationDepartment of Infectious Disease Research
A researcher / Research focus
We aim to study pathogenesis of infectious diseases to develop diagnosis and treatment methods.
The WHO estimates that there are more than 300 million people who are infected with the hepatitis virus all over the world. Hepatitis virus infection contributes to onset of cirrhosis and liver cancer, killing more than 1 million people each year. Japan is no exception to this situation, and hepatitis virus infection has become a serious public health problem. Our department attempts to investigate how the hepatitis virus can persist in hepatocytes and cause cirrhosis or hepatocellular carcinoma. By making a full investigation of the mechanism for enabling the sustained infection of the virus in hepatocytes and subsequent onset of the disease, we will explore clues for the development of methods for eliminating the virus, predicting its severity and preventing the progression of the disease.
This is a new research department established in 2021. Currently, we are in the process of setting up a laboratory.
We will update information on our website as we make progress in research and obtain achievement.
In Japan, the hepatitis B virus and hepatitis C virus are the two major hepatitis viruses that cause cirrhosis and hepatocellular carcinoma. The hepatitis B virus and hepatitis C virus are viruses that have DNA and RNA in their genomes, respectively, and are virologically different viruses. For the latter virus, which is the hepatitis C virus, several very good antiviral agents have been put into practical use in the last 10 years, and it has become a realistic goal to eliminate the virus from the liver. For the former virus, which is the hepatitis B virus, on the other hand, reverse transcription inhibitors are generally used as antiviral agents. The 2012 discovery of a receptor essential for the hepatitis B virus to infect cells has led to a rapid understanding of the viral life cycle in hepatocytes, especially understanding of the entry process of the hepatitis B virus into hepatocytes. Based on this basic information, drugs that block the invasion of viruses have been developed and are being used for treatment.
The hepatitis B virus is able to contain double-stranded covalently closed circular DNA called cccDNA in the nucleus of hepatocytes (Fig. 1). Although reverse transcriptase inhibitors are very good antiviral agents, they cannot eliminate cccDNA from infected hepatocytes once they have been generated, and if treatment is interrupted, the virus may be reproduced, starting from the cccDNA. New entry inhibitors also have the same weaknesses. Therefore, how to control cccDNA is extremely important for elimination of the virus from the body, and it is a major issue for the development of new antiviral agents.
An analysis of carcinogenic cells by the hepatitis B virus revealed that the DNA of the hepatitis B virus is integrated into the hepatocyte genome in most of the carcinogenic cells (Phenomenon of viral genome insertion) (Fig. 2).
This phenomenon is currently assumed to be caused by partially single-stranded viral DNA (RC-DNA) formed after reverse transcription or damaged cccDNA integrated into the host genome by some mechanism and stabilized.
The hepatitis B virus has genes (HBx, etc.) that have been suggested to have carcinogenic activity. It is assumed that constitutive expression of viral oncogenes from these genomic loci in which the oncogene is inserted promotes oncogenic transformation.
In our department, we will study how cccDNA lurks in hepatocytes and how viral genome insertion occurs and causes hepatocytes to become cancerous. Based on the basic information obtained, we will attempt to find clues for the development of new diagnostic methods and therapeutic agents.
Besides themes such as cccDNA and viral genome insertion, we plan to engage in research on various infectious pathologies. This department has just been launched, and we appreciate your assistance and support.