A cell-permeable peptide inhibits hepatitis C virus replication by sequestering IRES transacting factors.
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.
Fontanes
Vanessa
V
Department of Microbiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Raychaudhuri
Santanu
S
Dasgupta
Asim
A
D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001324:Autoantigens / Q000235:genetics; D002460:Cell Line; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D038941:Polypyrimidine Tract-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000187:drug effects; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects*; D000097585:SS-B Antigen
D000998:Antiviral Agents; D001324:Autoantigens; D010455:Peptides; D038941:Polypyrimidine Tract-Binding Protein; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C501903:PCBP2 protein, human