Hepatitis C virus RNA dimerization is mediated by kissing interactions

CHED 850

Kailey A. Ruszkowski, ruszkowskik@duq.edu, Sumangala S Shetty, shettys@duq.edu, and Mihaela Rita Mihailescu. Department of Chemistry and Biochemistry, Duquesne University, 600 Forbes Ave, 308 Mellon Hall, Pittsburgh, PA 15282
Worldwide, approximately 170 million people are chronically infected with the hepatitis C virus (HCV). The infection, for which there is no known effective treatment, has been linked to liver failure, cirrhosis and hepatocellular carcinoma. HCV, a member of the Flaviviridae family, consists of a 9.5 kb single-stranded RNA of positive polarity whose replication is highly error-prone. The viral RNA genome is comprised of a 5' untranslated region (5'-UTR), a single open reading frame (ORF), and a 3'-UTR. The 3'-UTR consists of four specific regions: a small, highly variable sequence, a long poly-U tract, a polypyrimidine tract, and finally, a highly conserved 98 nucleotide sequence, referred to as the X tail. This highly conserved X-tail has previously been shown to be essential for viral RNA replication and, more recently it has been shown to dimerize in the presence of the HCV core protein. In this study, we use biophysical techniques to characterize the dimerization the HCV X-tail RNA and we show that this process occurs via a kissing complex intermediate.