Hepatitis C virus core protein binds to a DEAD box RNA helicase.
Approximately 4 million Americans are infected with the hepatitis C virus (HCV), making it a major cause of chronic liver disease. Because of the lack of an efficient cell culture system, little is known about the interaction between HCV and host cells. We performed a yeast two-hybrid screen of a human liver cell cDNA library with HCV core protein as bait and isolated the DEAD box protein DBX. DBX has significant amino acid sequence identity to mouse PL10, an ATP-dependent RNA helicase. The binding of DBX to HCV core protein occurred in an in vitro binding assay in the presence of 1 M NaCl or detergent. When expressed in mammalian cells, HCV core protein and DBX were co-localized at the endoplasmic reticulum. In a mutant strain of Saccharomyces cerevisiae, DBX complemented the function of Ded1p, an essential DEAD box RNA helicase. HCV core protein inhibited the growth of DBX-complemented mutant yeast but not Ded1p-expressing yeast. HCV core protein also inhibited the in vitro translation of capped but not uncapped RNA. These findings demonstrate an interaction between HCV core protein and a host cell protein involved in RNA translation and suggest a mechanism by which HCV may inhibit host cell mRNA translation.
Mamiya
N
N
Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Worman
H J
HJ
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D053487:DEAD-box RNA Helicases; D005656:Fungal Proteins / Q000378:metabolism; D006367:HeLa Cells; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000235:genetics; D020365:RNA Helicases / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D014162:Transfection; D014758:Viral Core Proteins / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C059787:D1Pas1 protein, mouse; C492152:DED1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases