title: Alteration of copper-zinc superoxide dismutase 1 expression by influenza A virus is correlated with virus replication.
abstract: Viruses have evolved mechanisms designated to potentiate virus replication by modulating the physiological condition of host cells. The generation of reactive oxygen species (ROS) during infection with influenza virus A (IAV) is a well-established mechanism in animals, but little is known about the generation of ROS in in vitro cell culture models and about its role in virus replication. We show here that IAV H1N1 infected human alveolar cells increased superoxide anion level mainly by suppressing the copper-zinc superoxide dismutase 1 (SOD1) gene, and that the SOD1-controlled generation of ROS was tightly correlated with virus replication. The transcription factor Sp1, which is a major element of the proximal region of the sod1 promoter, was slightly downregulated at the transcriptional level during IAV infection, and subsequently modulated by post-translational control. A gradual reduction of whole Sp1 was largely responsible for the repression of sod1 transcription with increasing time post-infection, and their rescue by the proteasome inhibitor, MG132, proved the involvement of proteasomal degradation in Sp1 regulation during IAV infection. Furthermore, we observed that expression of viral polymerase PB1 was inversely proportional to SOD1 level. The antioxidant N-acetyl-cysteine (NAC) neutralized IAV-mediated oxidative stress, and either NAC treatment or sod1 transfection considerably diminished viral polymerase activity. These data indicate that IAV-induced SOD1 repression, which may cause impaired redox balance in host cells, can be attributed, at least in part, to enhance viral replication.
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Chul-Woong
authors.initials: CW
authors.lastname: Pyo
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Nary
authors.initials: N
authors.lastname: Shin
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Jung
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Joon Hwan
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea. Electronic address: sychoi@korea.ac.kr.
authors.forename: Sang-Yun
authors.initials: SY
authors.lastname: Choi
mesh_terms: D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000201:enzymology* / Q000821:virology*; D013223:Statistics as Topic; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014779:Virus Replication / Q000502:physiology*
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Influenza; ROS; SOD1; Sp1