Discovery of new Hepatitis C virus mechanism

July 27, 2016

Researchers at Osaka University, Japan uncovered the mechanisms that suppress the propagation of the hepatitis C virus (HCV) with the potential of improving pathological liver conditions. Using model mice, they confirmed that when a certain enzyme is inhibited, HCV particle production is reduced leading to an improvement of pathological liver conditions. They thereby identified a new drug target for the development of new HCV drugs.

About 200 million people around the world are infected with the HCV virus. HCV infection may cause fatty liver, hepatic fibrosis and liver cancer. In Japan, the HCV virus is the main cause for viral liver cancer, constituting 70% of liver cancers. Although the recent development of effective drugs targeting HCV replicative enzymes has enabled the elimination of HCV, challenges remain including the emergence of resistant viruses and the development of liver cancer after virus elimination. So far it was known that the cleavage of the HCV core protein by the enzyme signal-peptide peptidase (SPP) in infected host cells played an important role in the formation of viral particles and the development of pathological liver conditions. However, the details of this mechanism were not understood.

A research group led by Toru Okamoto, assistant professor and Yoshiharu Matsuura, professor at Research Institute for Microbial Diseases, Osaka University has now discovered that when the enzyme SPP is inhibited, HCV particle production is reduced resulting in an improvement of pathological liver conditions.

The researchers found a chemical compound that inhibits the SPP enzyme in the y-secretase inhibitor which is currently in the development process for Alzheimer's disease treatment. They also discovered that the immature core proteins which are not cleaved by SPP are recognized by the enzyme TRC8 and quickly degraded. If this degradation process is suppressed, cellular damage is strongly induced by endoplasmic reticulum stress (ER stress). The endoplasmic reticulum is central to protein biosynthesis and in a state of ER stress, the proteins synthesizing there are unable to fold up correctly thereby causing cell damage. This degradation process can therefore be considered as a quality control mechanism for new proteins. When the researchers administered the SPP inhibitor to model mice, HCV particle production was significantly reduced, improving HVC pathologic conditions such as insulin resistance and fatty liver.

The results of this study suggest the development of SPP inhibitors as a new hepatitis C drug. In addition, the observed protein quality control mechanism via SPP/TRC8 is thought to be related to other diseases as well thereby being potentially useful for the drug development for a variety of diseases.
This research was featured in the electronic version of Nature Communications on Wednesday, May 4, 2016 (British Time).

Osaka University

Related Hepatitis Articles from Brightsurf:

Busting Up the Infection Cycle of Hepatitis B
Researchers at the University of Delaware have gained new understanding of the virus that causes hepatitis B and the ''spiky ball'' that encloses its genetic blueprint.

Liver cancer: Awareness of hepatitis D must be raised
Scientists from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) have studied the most serious consequence of chronic hepatitis: hepatocellular carcinoma.

Hepatitis B: New therapeutic approach may help to cure chronic hepatitis B infection
Researchers at Helmholtz Zentrum München, Technical University of Munich (TUM) and the German Center for Infection Research (DZIF) have developed a novel therapeutic approach to cure chronic hepatitis B.

Anti-hepatitis medicine surprises
A new effective treatment of hepatitis C not only combats the virus, but is also effective against potentially fatal complications such as reduced liver functioning and cirrhosis.

Nanotechnology delivers hepatitis B vaccine
X-ray imaging shows that nanostructured silica acts as a protective vehicle to deliver intact antigen to the intestine so that it can trigger an immune response.

Checkmate for hepatitis B viruses in the liver
Researchers at Helmholtz Zentrum München and the Technical University of Munich, working in collaboration with researchers at the University Medical Center Hamburg-Eppendorf and the University Hospital Heidelberg, have for the first time succeeded in conquering a chronic infection with the hepatitis B virus in a mouse model.

How common is Hepatitis C infection in each US state?
Hepatitis C virus infection is a major cause of illness and death in the United States and injection drug use is likely fueling many new cases.

New strains of hepatitis C found in Africa
The largest population study of hepatitis C in Africa has found three new strains of the virus circulating in the general population in sub-Saharan Africa.

High stability of the hepatitis B virus
At room temperature, hepatitis B viruses (HBV) remain contagious for several weeks and they are even able to withstand temperatures of four degrees centigrade over the span of nine months.

Findings could lead to treatment of hepatitis B
Researchers have gained new insights into the virus that causes hepatitis B -- a life-threatening and incurable infection that afflicts more than 250 million people worldwide.

Read More: Hepatitis News and Hepatitis Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to