Hepatitis C virus core-derived peptides inhibit genotype 1b viral genome replication via interaction with DDX3X.
The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16-36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent protein (GFP) fusions to HCV core protein residues 16-36, but not by GFP fusions to core protein residues 16-35 or 16-34. Notably, the inhibition of HCV replication due to expression of the GFP fusion to HCV core protein residues 16-36 can be reversed by overexpression of DDX3X. These results suggest that the protein interface on DDX3X that binds the HCV core protein is important for replicon maintenance. However, infection of HuH-7 cells by HCV viruses of genotype 2a (JFH1) was not affected by expression of the GFP fusion protein. These results suggest that the role of DDX3X in HCV infection involves aspects of the viral life cycle that vary in importance between HCV genotypes.
Sun
Chaomin
C
California Institute for Quantitative Biosciences, University of California, Berkeley, California, USA.
Pager
Cara T
CT
Luo
Guangxiang
G
Sarnow
Peter
P
Cate
Jamie H D
JH
D020816:Amino Acid Motifs; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D016679:Genome, Viral; D005838:Genotype; D016174:Hepacivirus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D010455:Peptides; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases