Selective binding of hepatitis C virus core protein to synthetic oligonucleotides corresponding to the 5 ' untranslated region of the viral genome

Although it is assumed that hepatitis C virus (HCV) core protein binds with viral RNA to form a nucleocapsid, little is known about the resulting mole cular interactions. We utilized surface plasmon resonance technology to stu dy the structural basis of the affinity and the preference of the interacti on between HCV core protein and oligonucleotides derived from the Viral gen ome. Among the 10 oligonucleotides corresponding to the 5' untranslated reg ion (5'UTR) of the tested HCV genome, the real-time analysis of sensorgrams indicated that the core protein binds most efficiently and stably to the 3 1-nucleotide-long sequence of the loop IIId domain, whose secondary structu re is highly conserved not only among different HCV genotypes but also amon g pestiviruses. There also could be some interactions of the core protein w ith the loop I domain and the region of nt 23-41. The kinetic profiles, tog ether with those obtained in experiments using single- and double-stranded polymeric oligonucleotides, suggest a multimerization of the core protein i n solution. These newly characterized properties could provide a basis for understanding the pathway of the viral nucleocapsid assembly. (C) 2000 Acad emic Press.