Study reveals the liver's 'weak spot' for hepatitis B virus replication

February 13, 2018, Agency for Science, Technology and Research (A*STAR), Singapore
Study reveals the liver’s ‘weak spot’ for hepatitis B virus replication
In the absence of protective proteins Slug and SOX7, hepatitis B infection thrives in liver cells, indicated by green staining in this image. Credit: A*STAR Singapore Immunology Network

In a surprising discovery, researchers from the Singapore Immunology Network (SIgN), A*STAR, have found that the liver is the main site of hepatitis B (HBV) replication—not only because it contains material that helps the virus proliferate, but also because most other tissues of the body contain proteins that actively repress HBV replication.

"We've been working on this project for a number of years because HBV is very prevalent in Asia," says Ee Chee Ren, leader of the SIgN team that made the discovery.

"HBV enters the through specific receptors and then deposits its genetic material into the nucleus," explains SIgN's Hui Ling Ko, the paper's first author. The viral DNA then hijacks the host cell's machinery to make new copies of HBV. While it's known that liver contain factors that facilitate HBV replication, Ko and her team found that the cells also lack functional levels of the proteins Slug and SOX7. These proteins are found in most other human tissues, where they bind to the HBV genome and block the binding of the cells' proteins that initiate and promote viral replication. "Slug and SOX7 are involved in embryonic development and that's when they're most active," says Ko. After development, it is thought that the proteins are no longer required in the liver, and so get 'turned off.'

The team is now using tools including CRISPR-Cas9, the pioneering gene editing technology, to produce cells without any functioning Slug or SOX7 proteins. This nullifies the cells' defenses against HBV infection so that they can be used to test the efficacy of new drugs. "The reason for the very successful development of antiviral drugs for hepatitis C was the availability of robust, cell-based screening assays. Hepatitis B has always been lacking in this area," says Ren. "When we introduce HBV into these Slug-deficient cell lines, they show a large increase in the viral load. This provides us with a dramatically improved platform to create a drug screening assay for HBV." 

The SIgN team made another unexpected discovery during their studies: human colon, lung and stomach cells also lack Slug and SOX7. The scientists are now collaborating with clinicians at Singapore General Hospital to launch a thorough investigation into whether these tissues could act as a hidden reservoir of HBV, potentially complicating disease treatment.

Explore further: Hepatitis therapy: Kupffer cells adjust the balance between pathogen control and hepatocyte regenera

More information: Hui Ling Ko et al. Identification of Slug and SOX7 as transcriptional repressors binding to the hepatitis B virus core promoter, Journal of Hepatology (2017). DOI: 10.1016/j.jhep.2017.08.033

Related Stories

Hepatitis therapy: Kupffer cells adjust the balance between pathogen control and hepatocyte regenera

January 17, 2018
Inflammation of the liver can result from different causes. Besides infections with hepatitis B virus (HBV) and hepatitis C virus (HCV), other viruses such as cytomegalovirus (CMV) are able to trigger acute hepatitis. Sometimes ...

Effect of gut bacteria on specific immune cells underlies persistent liver inflammation

January 16, 2018
Persistent liver inflammation in sufferers of chronic viral hepatitis is likely caused by interactions between pro-inflammatory immune cells in the liver and products from gut bacteria, according to new work involving A*STAR ...

Study builds understanding of hepatitis C virus replication

February 23, 2015
Hepatitis C virus infection is a common cause of liver disease and of liver cancer in the United States. Through a new study that explores one aspect of how the virus hijacks host cell machinery to replicate itself, UNC Lineberger ...

Hepatitis C virus: How viral proteins interact in human cells

May 8, 2014
Scientists at the Helmholtz Zentrum München have for the first time decrypted the interaction network of hepatitis C virus proteins in living human cells. Their findings will contribute to a better understanding of the mechanisms ...

Scientists established a comprehensive protein interactions map of the replication machinery of a chronic virus

December 20, 2017
Chronic viral infections like HIV or hepatitis are among the biggest threats to human health worldwide. While an acute viral infection usually results in full recovery and effective immune memory, chronic viruses evade the ...

Recommended for you

Deadly Rift Valley fever: New insight, and hope for the future

July 19, 2018
Health control measures alone could be ineffective in the long term fight against the deadly Rift Valley fever which affects both humans and animals, a new study in the journal PNAS reports.

New guidelines to diagnose, manage rare endocrine disorders

July 19, 2018
International guidelines have been published for the first time to help doctors around the globe diagnose and manage patients with a very rare set of endocrine diseases known as pseudohypoparathyroidism and its related disorders, ...

Overuse of antibiotics not what the doctor ordered

July 19, 2018
With increased use of antibiotics worldwide linked to growing antibiotic resistance, a world-first study co-authored by a QUT researcher has highlighted the growing impact of non-prescription supply of antibiotics in community ...

Alcohol-related cirrhosis deaths skyrocket in young adults

July 18, 2018
Deaths from cirrhosis rose in all but one state between 1999-2016, with increases seen most often among young adults, a new study shows.

Hidden blood in feces may signal deadly conditions

July 17, 2018
(HealthDay)—Even if it's not visible to the naked eye, blood in the stool can be serious—a sign of a potentially fatal disease other than colon cancer, new research suggests.

Childhood abuse linked to greater risk of endometriosis, study finds

July 17, 2018
Endometriosis, a painful condition that affects one in 10 reproductive-age women in the U.S., has been linked to childhood physical and sexual abuse, according to findings published today in the journal Human Reproduction.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.