Combating hepatitis C virus by targeting microRNA-122 using locked nucleic acids.

MicroRNAs have been predicted to regulate the stability and translation of many target mRNAs that are involved in modulating disease outcome. Thus, valuable strategies to enhance or to diminish the function of microRNAs are needed to manipulate microRNA-mediated target gene expression. Recently, it has become apparent that one class of antisense oligonucleotides, locked nucleic acids, can be used to sequester microRNAs in the liver of a variety of animals including humans, opening the possibility of applying locked nucleic acid-mediated gene therapy.

Masking the 5' terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex.

Hepatitis C virus subverts liver-specific microRNA, miR-122, to upregulate viral RNA abundance in both infected cultured cells and in the liver of infected chimpanzees. These findings have identified miR-122 as an attractive antiviral target. Thus, it is imperative to know whether a distinct functional complex exists between miR-122 and the viral RNA versus its normal cellular target mRNAs.

The zinc finger antiviral protein acts synergistically with an interferon-induced factor for maximal activity against alphaviruses.

Type I interferons (IFNs) signal through specific receptors to mediate expression of genes, which together confer a cellular antiviral state. Overexpression of the zinc finger antiviral protein (ZAP) imparts a cellular antiviral state against Retroviridae, Togaviridae, and Filoviridae virus family members. Since ZAP expression is induced by IFN, we utilized Sindbis virus (SINV) to investigate the role of other IFN-induced factors in ZAP's inhibitory potential.

Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics.

Background & Aims: Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Current therapy with pegylated interferon alpha (IFN-alpha) in combination with ribavirin is associated with adverse effects and often fails to induce a sustained response. IFN-lambdas, recently discovered IFN gene family members, exhibit antiviral and cell stimulatory activities similar to IFN-alpha.