A class II phosphoinositide 3-kinase plays an indispensable role in hepatitis C virus replication.
Phosphoinositides function as fundamental signaling molecules and play roles in diverse cellular processes. Certain types of viruses may employ host cell phosphoinositide signaling systems to facilitate their replication cycles. Here we demonstrate that the β isoform of class II PI3K (PI3K-C2β) plays an indispensable role in hepatitis C virus (HCV) propagation in human hepatocellular carcinoma cells. Knockdown of PI3K-C2β abrogated HCV propagation in the cell. Using an HCV replicon system, we found that knockdown of PI3K-C2β substantially repressed the full-genome replication, while showing relatively small reductions in sub-genome replication, in which structural proteins including core protein were deleted. We also found that HCV core protein showed the binding activity towards D4-phosphorylated phosphoinositides and overlapped localization with phosphatidylinositol 3,4-bisphosphate in the cell. These results suggest that the phosphoinositide generated by PI3K-C2β plays an indispensable role in the HCV replication cycle through the binding to HCV core protein.
Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. Electronic address: tmaehama@nih.go.jp.
Tomohiko
T
Maehama
Masayoshi
M
Fukasawa
Tomoko
T
Date
Takaji
T
Wakita
Kentaro
K
Hanada
D006528:Carcinoma, Hepatocellular / Q000821:virology*; D045744:Cell Line, Tumor; D058541:Class II Phosphatidylinositol 3-Kinases; D055785:Gene Knockdown Techniques; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D014758:Viral Core Proteins / Q000378:metabolism; D014779:Virus Replication
D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D019869:Phosphatidylinositol 3-Kinases; D058541:Class II Phosphatidylinositol 3-Kinases; C502616:PIK3C2B protein, human
Hepatitis C virus (HCV); Phosphoinositide; Phosphoinositide 3-kinase (PI3K)