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.
MicroRNAs are involved in regulating the expression of genes in cells, usually by blocking the production of key proteins or by destabilising the messenger RNAs that encode the cell's proteins as it grows and divides. Normally they act by down regulating 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 stabilisation, 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 Doctor Stanley M. Lemon. "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 down regulates gene expression to up regulate the stability of its RNA and expression of viral proteins needed for its lifecycle. It is a classic example of how viruses subvert normally beneficial functions of the cell to their own nefarious purposes."
Work by 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 destabilises the viral genome, accelerating its degradation in the liver.
MEDICA.de; Source: University of North Carolina School of Medicine