Role of RNA Structures in Genome Terminal Sequences of the Hepatitis C Virus for Replication and Assembly

ABSTRACT Hepatitis C virus (HCV) is a positive-strand RNA virus replicating its genome via a negative-strand [(−)] intermediate. Little is known about replication signals residing in the 3′ end of HCV (−) RNA. Recent studies identified seven stem-loop structures (SL-I′, -IIz′, -IIy′, -IIIa′, -IIIb′, -IIIcdef′, and -IV′) in this region. In the present study, we mapped the minimal region required for RNA replication to SL-I′ and -IIz′, functionally confirmed the SL-IIz′ structure, and identified SL-IIIa′ to -IV′ as auxiliary replication elements. In addition, we show that the 5′ nontranslated region of the genome most likely does not contain cis-acting RNA structures required for RNA packaging into infectious virions.

[1]  M. Figlerowicz,et al.  Structural domains of the 3'-terminal sequence of the hepatitis C virus replicative strand. , 2008, Biochemistry.

[2]  Catherine L Jopling,et al.  Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. , 2008, Cell host & microbe.

[3]  R. Bartenschlager,et al.  Efficient trans-Encapsidation of Hepatitis C Virus RNAs into Infectious Virus-Like Particles , 2008, Journal of Virology.

[4]  M. Binder,et al.  Identification of Determinants Involved in Initiation of Hepatitis C Virus RNA Synthesis by Using Intergenotypic Replicase Chimeras , 2007, Journal of Virology.

[5]  Meehyein Kim,et al.  Structural requirements for assembly and homotypic interactions of the hepatitis C virus core protein. , 2006, Virus research.

[6]  Eva Herrmann,et al.  The Level of CD81 Cell Surface Expression Is a Key Determinant for Productive Entry of Hepatitis C Virus into Host Cells , 2006, Journal of Virology.

[7]  Ryosuke Suzuki,et al.  Down-regulation of the internal ribosome entry site (IRES)-mediated translation of the hepatitis C virus: critical role of binding of the stem-loop IIId domain of IRES and the viral core protein. , 2006, Virology.

[8]  P. Sarnow,et al.  Modulation of Hepatitis C Virus RNA Abundance by a Liver-Specific MicroRNA , 2005, Science.

[9]  R. Bartenschlager,et al.  Production of infectious hepatitis C virus in tissue culture from a cloned viral genome , 2005, Nature Medicine.

[10]  Ralf Bartenschlager,et al.  Kissing-Loop Interaction in the 3′ End of the Hepatitis C Virus Genome Essential for RNA Replication , 2005, Journal of Virology.

[11]  K. Timani,et al.  Two cis-acting elements in negative RNA strand of Hepatitis C virus involved in synthesis of positive RNA strand in vitro. , 2005, Acta virologica.

[12]  Ralf Bartenschlager,et al.  Novel insights into hepatitis C virus replication and persistence. , 2004, Advances in virus research.

[13]  C. Reusken,et al.  Analysis of hepatitis C virus/classical swine fever virus chimeric 5'NTRs: sequences within the hepatitis C virus IRES are required for viral RNA replication. , 2003, The Journal of general virology.

[14]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[15]  Dongsheng Li,et al.  Amino acids 1-20 of the hepatitis C virus (HCV) core protein specifically inhibit HCV IRES-dependent translation in HepG2 cells, and inhibit both HCV IRES- and cap-dependent translation in HuH7 and CV-1 cells. , 2003, The Journal of general virology.

[16]  S. Lemon,et al.  3′ Nontranslated RNA Signals Required for Replication of Hepatitis C Virus RNA , 2003, Journal of Virology.

[17]  G. Luo,et al.  Role of the 5′-Proximal Stem-Loop Structure of the 5′ Untranslated Region in Replication and Translation of Hepatitis C Virus RNA , 2003, Journal of Virology.

[18]  Catherine H. Wu,et al.  Secondary Structure and Hybridization Accessibility of Hepatitis C Virus 3′-Terminal Sequences , 2002, Journal of Virology.

[19]  M. Kieny,et al.  Secondary Structure of the 3′ Terminus of Hepatitis C Virus Minus-Strand RNA , 2002, Journal of Virology.

[20]  R. Bartenschlager,et al.  Genetic Analysis of Sequences in the 3′ Nontranslated Region of Hepatitis C Virus That Are Important for RNA Replication , 2002, Journal of Virology.

[21]  O. Yamada,et al.  Autogenous translational inhibition of core protein: implication for switch from translation to RNA replication in hepatitis C virus. , 2002, Virology.

[22]  Yoon Ki Kim,et al.  Domains I and II in the 5' nontranslated region of the HCV genome are required for RNA replication. , 2002, Biochemical and biophysical research communications.

[23]  R. Bartenschlager,et al.  Sequences in the 5′ Nontranslated Region of Hepatitis C Virus Required for RNA Replication , 2001, Journal of Virology.

[24]  H. Ushijima,et al.  Selective binding of hepatitis C virus core protein to synthetic oligonucleotides corresponding to the 5' untranslated region of the viral genome. , 2000, Virology.

[25]  Y. Matsuura,et al.  Interaction of Hepatitis C Virus Core Protein with Viral Sense RNA and Suppression of Its Translation , 1999, Journal of Virology.

[26]  A. Sherker,et al.  Specific in vitro association between the hepatitis C viral genome and core protein , 1999, Journal of medical virology.

[27]  M. Yanagi,et al.  In vivo analysis of the 3' untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  M. Honda,et al.  A Phylogenetically Conserved Stem-Loop Structure at the 5′ Border of the Internal Ribosome Entry Site of Hepatitis C Virus Is Required for Cap-Independent Viral Translation , 1999, Journal of Virology.

[29]  A. Nomoto,et al.  Genetic analysis of internal ribosomal entry site on hepatitis C virus RNA: implication for involvement of the highly ordered structure and cell type-specific transacting factors. , 1997, Virology.

[30]  E. Frolova,et al.  Packaging signals in alphaviruses , 1997, Journal of virology.

[31]  A. Nomoto,et al.  Internal ribosome entry site within hepatitis C virus RNA , 1992, Journal of virology.

[32]  R. Bartenschlager,et al.  A short cis‐acting sequence is required for hepatitis B virus pregenome encapsidation and sufficient for packaging of foreign RNA. , 1990, The EMBO journal.

[33]  A. Miller,et al.  Retroviral RNA packaging: sequence requirements and implications. , 1990, Current topics in microbiology and immunology.

[34]  T. Gadek,et al.  Evidence for specificity in the encapsidation of Sindbis virus RNAs , 1989, Journal of virology.