Hepatitis C virus non-structural protein-2 activates CXCL-8 transcription through NF-kappaB.
Hepatitis C is a devastating disease worldwide. Proteins encoded by the etiologic agent, hepatitis C virus (HCV), are believed to play important roles in HCV-associated pathogenesis. However, the biological functions of the non-structural protein-2 (NS2) encoded by HCV are not well characterized. Here, we show that HCV NS2 protein activates CXCL-8 (interleukin-8, IL-8) transcription in HepG2 cells as measured by reverse transcription-polymerase chain reaction and IL-8 promoter-luciferase reporter assays. Furthermore, when the kappaB site on the IL-8 promoter was eliminated by mutagenesis or when intracellular NF-kappaB activity was suppressed by an inhibitor, NS2 did not activate the IL-8 promoter, suggesting a role of NF-kappaB in this process. These results prompted us to hypothesize that HCV NS2 might be able to activate NF-kappaB. This hypothesis was tested by determination of NF-kappaB-driven reporter gene expression and NF-kappaB p65 subunit subcellular localization after HCV NS2 expression. Indeed, NS2 could up-regulate NF-kappaB-driven luciferase activity and was associated with p65 nuclear localization. These results demonstrate that HCV NS2 up-regulates IL-8 transcription through NF-kappaB. This newly identified function increases our understanding of the role of HCV NS2 protein in virus-host interactions.
Oem
J-K
JK
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada.
Jackel-Cram
C
C
Li
Y-P
YP
Kang
H-N
HN
Zhou
Y
Y
Babiuk
L A
LA
Liu
Q
Q
D019677:Artificial Gene Fusion; D001665:Binding Sites; D002460:Cell Line; D017930:Genes, Reporter; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D016296:Mutagenesis; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
D016209:Interleukin-8; D016328:NF-kappa B; C097010:NS2 protein, Hepatitis C virus; D017361:Viral Nonstructural Proteins; D008156:Luciferases