Stimulation of interferon-beta gene expression by human cytomegalovirus via nuclear factor kappa B and phosphatidylinositol 3-kinase pathway.
Infection of human foreskin fibroblast (HFF) cells with human cytomegalovirus (HCMV) induces the secretion of soluble factors including interferon (IFN)-beta that stimulates human leukocyte antigen (HLA) class I expression. In this study, the mechanism of IFN-beta induction by HCMV was investigated. In HCMV-infected HFF cells, IFN-beta secretion increased at 6h post infection (h.p.i.). Reverse transcription polymerase chain reaction (RT-PCR) analysis using ultra violet (UV)-inactivated HCMV indicated that viral gene expression is not necessary for the stimulation of IFN-beta. Stimulation of IFN-beta by HCMV infection was not blocked by cycloheximide, an inhibitor of protein synthesis, further suggesting that the expression of HCMV genes is not required for the stimulation of IFN-beta gene transcription. IFN-beta may be produced from virus-infected cells as an inflammatory response and nuclear factor kappa B (NF-kappaB) plays a central role in inflammatory response. HCMV failed to induce the IFN-beta expression, when the virus-infected cells were treated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB, or LY294002 and wortmannin, inhibitors of phosphatidylinositol 3-kinase (PI3-K). The result suggests that PI3-K and/or NF-kappaB may be related with the induction pathway of IFN-beta by HCMV.
Division of Life Sciences, College of Natural Sciences, and Biotechnology Research Institute, Chungbuk National University, 12 Gaeshindong, Cheongju, Chungbuk 361-763, South Korea. chlee@chungbuk.ac.kr
Gyu Cheol
GC
Lee
Hyun Ah
HA
Yi
Chan Hee
CH
Lee
D000730:Androstadienes / Q000494:pharmacology; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003587:Cytomegalovirus / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000821:virology; D015870:Gene Expression; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology; D014158:Transcription, Genetic; D000077191:Wortmannin
D000730:Androstadienes; D003513:Cycloheximide; D004791:Enzyme Inhibitors; D016899:Interferon-beta; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011500:Protein Synthesis Inhibitors; D011759:Pyrrolidines; D012333:RNA, Messenger; D012367:RNA, Viral; D013859:Thiocarbamates; D000077191:Wortmannin; C020972:pyrrolidine dithiocarbamic acid