Study builds understanding of hepatitis C virus replication

February 23, 2015, University of North Carolina at Chapel Hill School of Medicine

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 Comprehensive Cancer Center researchers have gained insight into the workings of a potential drug target for hepatitis C.

The study, published online Feb. 5 in the journal Cell Host & Microbe, explains the role of one small, but critical molecule called miR-122 in helping the virus replicate itself.

"This small host molecule is essential for C replication in the liver, but we have never fully understood how or why," said Stanley M. Lemon, MD, a UNC Lineberger member, a professor in the UNC School of Medicine Division of Infectious Diseases, and the principal investigator of the study. "This study gives us a pretty clear idea of what miR-122 is doing to promote the viral life cycle."

Made specifically by liver cells, miR-122 is a type of molecule called a microRNA. MicroRNAs are short RNA molecules that do not code for specific proteins, but rather regulate the production of proteins that are coded by much longer "messenger" RNAs made by the cell. Specifically, microRNAs down-regulate the translation of cellular messenger RNAs into proteins.

While the normal function of miR-122 is to down-regulate the expression of numerous proteins in the liver, the hepatitis C virus uses the molecule to promote its own reproduction. Specifically, the UNC Lineberger-led study found that miR-122 helps promote viral reproduction by directing the viral genome away from viral protein production and toward synthesis of more of the virus' own RNA.

The code carried by the viral RNA genome is used to make virus proteins as well as to make more RNA, Lemon said. And both proteins and RNA are needed for viral growth, but the hepatitis C genome can't do both at the same time.

"What we show in this study is that miR-122 shifts the genome from making viral protein to making more viral RNA," he said. "RNA synthesis is critical, and miR-122 optimizes it so production of new virus is maximized."

The finding builds on the previous understanding of the importance of miR-122 to hepatitis C, Lemon said. It was already known that miR-122 helps to protect the viral genome from being degraded by the host cell, but the molecule's full role in promoting viral replication wasn't appreciated.

 "This research builds on about 10 years of understanding that miR-122 is critical for the ability of hepatitis C to grow in the liver, and more recently, on the finding that miR-122 makes the viral RNA more stable by protecting it against degradation," Lemon said.

There is an effort to develop a new hepatitis C treatment that would block viral growth by inhibiting miR-122, and Lemon said the study's findings could help explain how those potential treatments could work.

And in general, he said it helps build a greater understanding of the virus' life cycle in the cell. Such research has helped bring other treatments into the clinic, such as several new hepatitis C drugs approved last year, on the heels of two others approved in 2011. All of the approved drugs block the actions of specific proteins needed by the hepatitis C virus to replicate.

"Such knowledge has contributed immeasurably to the development of new therapies that have recently entered the clinic," Lemon said of basic science research into the viral life cycle. "However, we have much to learn still about how this causes cancer, and how this can be prevented."

Explore further: Researchers discover how hepatitis C virus reprograms human liver cells

More information: "miR-122 Stimulates Hepatitis C Virus RNA Synthesis by Altering the Balance of Viral RNAs Engaged in Replication versus Translation." DOI: 10.1016/j.chom.2014.12.014

Related Stories

Researchers discover how hepatitis C virus reprograms human liver cells

December 18, 2012
Hepatitis C virus has evolved to invade and hijack the basic machinery of the human liver cell to ensure its survival and spread. Researchers at the University of North have discovered how hepatitis C binds with and repurposes ...

Hepatitis C virus survives by hijacking liver microRNA: study

January 2, 2012
Viral diseases are still one of the biggest challenges to medical science. Thanks to thousands of years of co-evolution with humans, their ability to harness the biology of their human hosts to survive and thrive makes them ...

miR-122: Loss of tiny liver molecule might lead to liver cancer

July 23, 2012
A new study shows that loss of a small RNA molecule in liver cells might cause liver cancer and that restoring the molecule might slow tumor growth and offer a new way to treat the disease.

Hepatitis B virus promotes oncogenesis through microRNA modulation

January 16, 2013
Viruses prompt oncogenic transformation by genetically altering infected cells. Several recent studies have demonstrated that viruses alter the expression of microRNAs, non-coding RNA molecules that can block the expression ...

Researchers discover how Hepatitis C virus persists for years

July 29, 2014
Hepatitis C virus (HCV) lingers in the human body for years, slowly damaging the liver and leading to liver diseases such as hepatitis, cirrhosis and liver cancer, which is often fatal. Research conducted at the University ...

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 ...

Recommended for you

Lung-on-a-chip simulates pulmonary fibrosis

May 25, 2018
Developing new medicines to treat pulmonary fibrosis, one of the most common and serious forms of lung disease, is not easy.

Reconstructing Zika's spread

May 24, 2018
The urgent threat from Zika virus, which dominated news headlines in the spring and summer of 2016, has passed for now. But research into how Zika and other mosquito-borne infections spread and cause epidemics is still very ...

Tick bite protection: New CDC study adds to the promise of permethrin-treated clothing

May 24, 2018
The case for permethrin-treated clothing to prevent tick bites keeps getting stronger.

Molecular network boosts drug resistance and virulence in hospital-acquired bacterium

May 24, 2018
In response to antibiotics, a gene regulation network found in the bacterium Acinetobacter baumannii acts to boost both virulence and antibiotic resistance. Edward Geisinger of Tufts University School of Medicine and colleagues ...

Past use of disinfectants and PPE for Ebola could inform future outbreaks

May 24, 2018
Data from the 2014 Ebola virus outbreak at two Sierra Leone facilities reveal daily usage rates for disinfectant and personal protective equipment, informing future outbreaks, according to a study published May 24, 2018 in ...

Early lactate measurements appear to improve results for septic patients

May 24, 2018
On October 1, 2015, the United States Centers for Medicare and Medicaid Services (CMS) issued a bundle of recommendations defining optimal treatment of patients suffering from sepsis, a life-threatening response to infection ...

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.