Researchers at the University of North have discovered how hepatitis C binds with and repurposes a basic component of cellular metabolism known as a microRNA to help protect and replicate the virus.
A cultured liver cancer cell infected with Hepatitis C. The virus, stained red, surrounds the blue-stained nucleus and is in the process of being reproduced by virus within the cytoplasm. Photo courtesy of Takahiro Masaki/UNC Lemon Lab
In a paper published online in the Proceedings of the National Academy of Sciences Dec. 17, researchers in the laboratory of Stanley M. Lemon, MD, professor of medicine and microbiology and immunology and member of UNC Lineberger Comprehensive Cancer Center, the Center for Translational Immunology, and the UNC Center for Infectious Disease, outline the critical role the microRNA known as miR-122 plays in the life cycle of the hepatitis C virus.
A chronic blood-borne virus that attacks the liver, hepatitis C infects more than four million in the United States and more than 130 million worldwide. Deaths from the infection surpass those due to HIV/AIDS in the U.S. The virus is currently the leading factor in liver transplantation and a major cause of liver cancer, the third most fatal cancer worldwide and the ninth most deadly in the United States. Chronic hepatitis virus infections factor into more than two-thirds of liver cancer deaths.
“There is no cancer in the United States that is increasing in incidence as fast as liver cancer, and that is because of hepatitis C,” said Dr. Lemon.
One question has been why hepatitis C virus specifically targets the liver. The research of Dr. Lemon and his colleagues points to the interaction between the hepatitis virus and miR-122 as the explanation.
The human genome contains around 1,000 microRNAs, strands of cellular material that play a diverse role in regulating gene expression and cellular metabolism. In a healthy liver cell, the microRNA miR-122 regulates the activity and decay of numerous cellular RNAs responsible for the production of proteins. It normally functions to block protein expression or to promote degradation of RNAs in the cell. The hepatitis C virus genome is entirely RNA, but miR-122 acts on it in a completely different manner - stabilizing it and enhancing its ability to produce viral proteins. In effect, it promotes and protects the invader.
“MicroRNAs almost always promote the degradation of cellular RNAs. This is actually stabilizing the viral RNA,” said Dr. Lemon.
While Dr. Lemon’s team has explored the manner in which hepatitis C exploits miR-122 to protect the viral RNA in previous publications, the new research suggests a much deeper bond between the microRNA and virus. Hepatitis C RNA contains a site that binds directly to the microRNA, and the team has shown that the presence of miR122 is actually crucial for functioning of the virus. Dr. Lemon believes the virus has evolved a unique dependency and that it requires the host’s microRNA to reproduce.
“It is a relationship that is unique to hepatitis C and not seen, as far as we know, with any other virus,” said Dr. Lemon.
Because of the importance of miR-122 to the replication of hepatitis C, the microRNA presents a promising target for new drugs. The pharmaceutical industry has already begun developing therapies that target miR-122. Dr. Lemon said that his research will help explain the underlying biology behind why these drugs work and suggest new possibilities for treatment by targeting other enzymes and proteins that play a role in the interactions between the virus and miR-122.
“If you target miR-122 with a therapeutic that blocks its function or sequesters it so it is no longer accessible to the virus, the replication of the virus is severely impaired,” said Dr. Lemon.
This work was supported by National Institutes of Health Grants R01-AI095690 and P20-CA150343 and the North Carolina University Cancer Research Fund.
William Davis | Source: EurekAlert!
Further information: www.unc.edu
More articles from Life Sciences:
Young killer cells protect against infectious mononucleosis
19.12.2013 | Universität Zürich
Scientists find a groovy way to influence specialisation of stem cells
19.12.2013 | Queen Mary University of London
Swimming microengines made from platinum and iron are highly efficient in removing organic pollutants from water using hydrogen peroxide.
Researchers from the Max Planck Institute for Intelligent Systems in Stuttgart have developed a new method for the active degradation of organic pollutants in solution by using swimming microengines.
The mobile microcleaners consist of an outer iron and an inner platinum layer, thereby combining two functionalities. Hydrogen peroxide, which must be ...
A 12-year study of massive stars has reaffirmed that our Galaxy has four spiral arms, following years of debate sparked by images taken by NASA's Spitzer Space Telescope that only showed two arms.
The new research, which is published online today [17 December] in the Monthly Notices of the Royal Astronomical Society, is part of the RMS Survey, which was launched by academics at the University of Leeds.
Astronomers cannot see what our Galaxy, which is called the Milky Way, looks like because we ...
In collaboration with the University of Basel, an international team of researchers has observed a strong energy loss caused by frictional effects in the vicinity of charge density waves.
This may have practical significance in the control of nanoscale friction. The results have been published in the scientific journal Nature Materials.
Friction is often seen as an adverse phenomenon that leads to wear and causes energy loss. Conversely, however, too little friction can be a disadvantage as well – ...
A new type of transistor that could make possible fast and low-power computing devices for energy-constrained applications such as smart sensor networks, implantable medical electronics and ultra-mobile computing is feasible, according to Penn State researchers.
Called a near broken-gap tunnel field effect transistor (TFET), the new device uses the quantum mechanical tunneling of electrons through an ultrathin energy barrier to provide high current at low voltage.
Penn State, the National Institute of Standards and Technology and IQE, a specialty wafer manufacturer, jointly presented their findings at ...
The team of Johannes Zuber at the IMP in Vienna, Austria, managed to overcome remaining key limitations of RNA interference (RNAi) - a unique method to specifically shut off genes.
By using an optimized design, the scientists were able to inhibit genes with greatly enhanced efficiency and accuracy. The new method facilitates the search for drug targets and improves the interpretation of experimental results.
The IMP will make this „RNAi toolkit“ available to researchers. Results of the study are published in ...
19.12.2013 | Life Sciences
19.12.2013 | Health and Medicine
19.12.2013 | Materials Sciences
19.12.2013 | Event News
11.12.2013 | Event News
10.12.2013 | Event News