title: Alteration in superoxide dismutase 1 causes oxidative stress and p38 MAPK activation following RVFV infection.
abstract: Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV). RVFV is a category A pathogen that belongs to the genus Phlebovirus, family Bunyaviridae. Understanding early host events to an infectious exposure to RVFV will be of significant use in the development of effective therapeutics that not only control pathogen multiplication, but also contribute to cell survival. In this study, we have carried out infections of human cells with a vaccine strain (MP12) and virulent strain (ZH501) of RVFV and determined host responses to viral infection. We demonstrate that the cellular antioxidant enzyme superoxide dismutase 1 (SOD1) displays altered abundances at early time points following exposure to the virus. We show that the enzyme is down regulated in cases of both a virulent (ZH501) and a vaccine strain (MP12) exposure. Our data demonstrates that the down regulation of SOD1 is likely to be due to post transcriptional processes and may be related to up regulation of TNFα following infection. We also provide evidence for extensive oxidative stress in the MP12 infected cells. Concomitantly, there is an increase in the activation of the p38 MAPK stress response, which our earlier published study demonstrated to be an essential cell survival strategy. Our data suggests that the viral anti-apoptotic protein NSm may play a role in the regulation of the cellular p38 MAPK response. Alterations in the host protein SOD1 following RVFV infection appears to be an early event that occurs in multiple cell types. Activation of the cellular stress response p38 MAPK pathway can be observed in all cell types tested. Our data implies that maintaining oxidative homeostasis in the infected cells may play an important role in improving survival of infected cells.
authors.affiliation: National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, Virginia, United States of America.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Narayanan
authors.forename: Taissia
authors.initials: T
authors.lastname: Popova
authors.forename: Michael
authors.initials: M
authors.lastname: Turell
authors.forename: Jessica
authors.initials: J
authors.lastname: Kidd
authors.forename: Jessica
authors.initials: J
authors.lastname: Chertow
authors.forename: Serguei G
authors.initials: SG
authors.lastname: Popov
authors.forename: Charles
authors.initials: C
authors.lastname: Bailey
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
authors.forename: Kylene
authors.initials: K
authors.lastname: Kehn-Hall
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012296:Rift Valley fever virus / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014709:Vero Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C000606290:SOD1 protein, human; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D048051:p38 Mitogen-Activated Protein Kinases