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Literature DB >> 19740508

A cell-permeable peptide inhibits hepatitis C virus replication by sequestering IRES transacting factors.

Vanessa Fontanes¹, Santanu Raychaudhuri, Asim Dasgupta.

Abstract

Hepatitis C virus (HCV) infection frequently leads to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. There is no effective therapy or vaccine available to HCV-infected patients other than interferon-ribavarin combination, which is effective in a relatively small percentage of infected patients. Our previous results have shown that a synthetic peptide (LAP) corresponding to the N-terminal 18 amino acids of the Lupus autoantigen (La) was a potent inhibitor of HCV IRES-mediated translation. We demonstrate here that LAP efficiently blocks HCV replication of infectious JFH1 virus in cell culture. Our data suggest that LAP forms complexes with IRES-transacting factors (ITAFs) PTB and PCBP2. LAP-mediated inhibition of HCV IRES-mediated translation in vitro could be fully rescued by recombinant PCB and PCBP2. Also transient expression of PTB / PCBP2 combination significantly restores HCV replication in LAP-inhibited cultures. These results suggest that ITAFs could be potential targets to block HCV replication.

Entities: CellLine Chemical Disease Gene Mutation Species

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Year: 2009 PMID： 19740508 PMCID： PMC2767405 DOI： 10.1016/j.virol.2009.08.012

Source DB: PubMed Journal: Virology ISSN： 0042-6822 Impact factor: 3.616

40 in total

Review 1. Identification of the major, parenteral non-A, non-B hepatitis agent (hepatitis C virus) using a recombinant cDNA approach.

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Journal: Semin Liver Dis Date: 1992-08 Impact factor: 6.115

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Authors: L B Blyn; J S Towner; B L Semler; E Ehrenfeld
Journal: J Virol Date: 1997-08 Impact factor: 5.103

4. Sequences within a small yeast RNA required for inhibition of internal initiation of translation: interaction with La and other cellular proteins influences its inhibitory activity.

Authors: S Das; D J Kenan; D Bocskai; J D Keene; A Dasgupta
Journal: J Virol Date: 1996-03 Impact factor: 5.103

5. The La antigen binds 5' noncoding region of the hepatitis C virus RNA in the context of the initiator AUG codon and stimulates internal ribosome entry site-mediated translation.

Authors: N Ali; A Siddiqui
Journal: Proc Natl Acad Sci U S A Date: 1997-03-18 Impact factor: 11.205

6. Structural determinant of human La protein critical for internal initiation of translation of hepatitis C virus RNA.

Authors: Tanmoy Mondal; Upasana Ray; Asit Kumar Manna; Romi Gupta; Siddhartha Roy; Saumitra Das
Journal: J Virol Date: 2008-10-01 Impact factor: 5.103

7. A cytoplasmic 57-kDa protein that is required for translation of picornavirus RNA by internal ribosomal entry is identical to the nuclear pyrimidine tract-binding protein.

Authors: C U Hellen; G W Witherell; M Schmid; S H Shin; T V Pestova; A Gil; E Wimmer
Journal: Proc Natl Acad Sci U S A Date: 1993-08-15 Impact factor: 11.205

8. La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate.

Authors: K Meerovitch; Y V Svitkin; H S Lee; F Lejbkowicz; D J Kenan; E K Chan; V I Agol; J D Keene; N Sonenberg
Journal: J Virol Date: 1993-07 Impact factor: 5.103

9. Interaction of polypyrimidine tract-binding protein with the 5' noncoding region of the hepatitis C virus RNA genome and its functional requirement in internal initiation of translation.

Authors: N Ali; A Siddiqui
Journal: J Virol Date: 1995-10 Impact factor: 5.103

10. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA.

Authors: J Pelletier; N Sonenberg
Journal: Nature Date: 1988-07-28 Impact factor: 49.962

15 in total

1. Poly(C)-binding protein 2 interacts with sequences required for viral replication in the hepatitis C virus (HCV) 5' untranslated region and directs HCV RNA replication through circularizing the viral genome.

Authors: Linya Wang; King-Song Jeng; Michael M C Lai
Journal: J Virol Date: 2011-06-01 Impact factor: 5.103

9. The 3' untranslated region of the rabies virus glycoprotein mRNA specifically interacts with cellular PCBP2 protein and promotes transcript stability.

Authors: Saiprasad Palusa; Christina Ndaluka; Richard A Bowen; Carol J Wilusz; Jeffrey Wilusz
Journal: PLoS One Date: 2012-03-16 Impact factor: 3.240

Review 10. Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses.

Authors: Richard E Lloyd
Journal: Virology Date: 2015-03-26 Impact factor: 3.616

A cell-permeable peptide inhibits hepatitis C virus replication by sequestering IRES transacting factors.

Review 1. Identification of the major, parenteral non-A, non-B hepatitis agent (hepatitis C virus) using a recombinant cDNA approach.

Review 2. Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease.

3. Requirement of poly(rC) binding protein 2 for translation of poliovirus RNA.

4. Sequences within a small yeast RNA required for inhibition of internal initiation of translation: interaction with La and other cellular proteins influences its inhibitory activity.

5. The La antigen binds 5' noncoding region of the hepatitis C virus RNA in the context of the initiator AUG codon and stimulates internal ribosome entry site-mediated translation.

6. Structural determinant of human La protein critical for internal initiation of translation of hepatitis C virus RNA.

7. A cytoplasmic 57-kDa protein that is required for translation of picornavirus RNA by internal ribosomal entry is identical to the nuclear pyrimidine tract-binding protein.

8. La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate.

9. Interaction of polypyrimidine tract-binding protein with the 5' noncoding region of the hepatitis C virus RNA genome and its functional requirement in internal initiation of translation.

10. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA.

1. Poly(C)-binding protein 2 interacts with sequences required for viral replication in the hepatitis C virus (HCV) 5' untranslated region and directs HCV RNA replication through circularizing the viral genome.

Review 2. Tinkering with translation: protein synthesis in virus-infected cells.

3. Targeting ribosome assembly on the HCV RNA using a small RNA molecule.

4. Identification of RNA-protein interaction networks involved in the norovirus life cycle.

5. Hepatitis C virus infection alters P-body composition but is independent of P-body granules.

Review 6. Hepatitis C virus translation inhibitors targeting the internal ribosomal entry site.

7. Hepatitis C virus RNA: molecular switches mediated by long-range RNA-RNA interactions?

8. PCBP2 enhances the antiviral activity of IFN-α against HCV by stabilizing the mRNA of STAT1 and STAT2.

9. The 3' untranslated region of the rabies virus glycoprotein mRNA specifically interacts with cellular PCBP2 protein and promotes transcript stability.

Review 10. Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses.