Mechanism explains how virus survives in the liver and how a new antiviral works
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 very difficult to target with medical treatment.
Scientists at the University of North Carolina at Chapel Hill, working with colleagues from the University of Colorado, have shown for the first time how a small RNA molecule that regulates gene expression in human liver cells has been hijacked by the hepatitis C virus to ensure its own survival – helping medical scientists understand why a new antiviral drug appears to be effective against the virus.
MicroRNAs are involved in regulating the expression of genes in cells, usually by blocking the production of key proteins or by destabilizing the messenger RNAs that encode the cell's proteins as it grows and divides. Normally they act by downregulating gene expression. The research team found that the binding of a prominent microRNA in liver cells, called miR-122, to the viral RNA results in its stabilization, promoting efficient replication of the virus genome in the liver and supporting the virus' lifecycle.
"The hepatitis C virus has done two very interesting things with miR-122," says Stanley M. Lemon, MD, professor of medicine and microbiology and immunology and a member of UNC Lineberger Comprehensive Cancer Center and the Center for Translational Immunology.
"First, it has evolved a unique relationship with a key regulator, since miR-122 represents about half of all microRNAs present in the liver. Second, the virus has usurped a process that usually downregulates gene expression to upregulate the stability of its RNA and expression of viral proteins needed for its lifecycle. It's a classic example of how viruses subvert normally beneficial functions of the cell to their own nefarious purposes."
Work by Dr. Lemon and his colleagues in 2005 helped to demonstrate that miR-122 was required for hepatitis C to replicate itself, but the mechanism was not understood. Now the UNC research team has shown how it works, which helps to explain how a new experimental antiviral drug target the virus. The drug, called an "antagomer", binds to miR-122 and sequesters it in the liver and thus destabilizes the viral genome, accelerating its degradation in the liver. Results of the most recent study are published in Proceedings of the National Academy of Sciences.
Scientists at the University of North Carolina School of Medicine have developed a way to embed light-responsive switches into proteins so that researchers can use lasers to manipulate protein movement and activity within living cells and animals.
Using this technique, the UNC team of scien ... more
A SARS-like virus found in Chinese horseshoe bats may be poised to infect humans without the need for adaptation, overcoming an initial barrier that could potentially set the stage for an outbreak according to a study at the University of North Carolina at Chapel Hill.
The work, led by Ralp ... more
In a first for medical science, University of North Carolina at Chapel Hill pharmacy researchers turn skin cells into cancer-hunting stem cells that destroy brain tumors known as glioblastoma - a discovery that can offer, for the first time in more than 30 years, a new and more effective tr ... more
Carolina’s vibrant people and programs attest to the University’s long-standing place among leaders in higher education since it was chartered in 1789 and opened its doors for students in 1795 as the nation’s first public university. Situated in the beautiful college town of Chapel Hill, N. ... more
If genes form the body's blueprint, then the layer of epigenetics decides which parts of the plan get built. Unfortunately, many cancers hijack epigenetics to modulate the expression of genes, thus promoting cancer growth and survival. A team of researchers led by Tatiana Kutateladze, PhD, ... more
A University of Colorado Cancer Center study presented at the American Association for Cancer Research Annual Meeting 2016 demonstrates the use of gas microbubbles to selectively attach to and float circulating tumor cells from blood samples, allowing analysis of the isolated cells.
"Microb ... more
Ben-Gurion University of the Negev and University of Colorado researchers have used a highly novel approach to create a dynamic ‘smart’ drug that is attentive to the degree of the inflammation. The three describe a novel creative development of an anti-inflammatory engineered protein in the ... more