title: Upregulation of Nrf2 expression by human cytomegalovirus infection protects host cells from oxidative stress.
abstract: NF-E2 related factor 2 (Nrf2) is a transcription factor that plays a key role(s) in cellular defence against oxidative stress. In this study, we showed that the expression of Nrf2 was upregulated in primary human foreskin fibroblasts (HFFs), following human cytomegalovirus (HCMV/HHV-5) infection. The expression of haem oxygenase-1, a downstream target of Nrf2, was also increased by HCMV infection, and this induction was suppressed in HFFs expressing a small hairpin RNA (shRNA) against Nrf2. The HCMV-mediated increase in Nrf2 expression was abolished when UV-irradiated virus was used or when the activity of casein kinase 2 was inhibited. Host cells infected by HCMV had higher survival rates following oxidative stress induced by buthionine sulfoximine compared with uninfected control cells, but this cell-protective effect was abolished by the use of Nrf2 shRNA. Our results suggest that HCMV-mediated activation of Nrf2 might be beneficial to the virus by increasing the host cell's ability to cope with oxidative stress resulting from viral infection and/or inflammation.
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Junsub
authors.initials: J
authors.lastname: Lee
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Kyungmi
authors.initials: K
authors.lastname: Koh
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Kyonggido 440-746, Korea.
authors.forename: Young-Eui
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Kyonggido 440-746, Korea.
authors.forename: Jin-Hyun
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Kim
mesh_terms: D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002470:Cell Survival; D003587:Cytomegalovirus / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000821:virology; D019610:Cytoprotection; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology* / Q000821:virology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D019328:Buthionine Sulfoximine; D051547:Heme Oxygenase-1