title: Reactive oxygen species activate NFκB (p65) and p53 and induce apoptosis in RVFV infected liver cells.
abstract: Rift Valley fever virus (RVFV) infection is often associated with pronounced liver damage. Previously, our studies revealed altered host phospho-signaling responses (NFκB, MAPK and DNA damage responses) in RVFV infected epithelial cells that correlated with a cellular stress response. Here, we report that RVFV infection of liver cells leads to an increase in reactive oxygen species (ROS). Our data suggests the presence of the viral protein NSs in the mitochondria of infected cells, hence contributing to early increase in ROS. Increased ROS levels correlated with activation of NFκB (p65) and p53 responses, which in conjunction with infection, was also reflected as macromolecular rearrangements observed using size fractionation of protein lysates. Additionally, we documented an increase in cytokine expression and pro-apoptotic gene expression with infection, which was reversed with antioxidant treatment. Collectively, we identified ROS and oxidative stress as critical contributors to apoptosis of liver cells during RVFV infection.
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Narayanan
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Moushimi
authors.initials: M
authors.lastname: Amaya
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Voss
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Myung
authors.initials: M
authors.lastname: Chung
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Benedict
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Gavin
authors.initials: G
authors.lastname: Sampey
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Kylene
authors.initials: K
authors.lastname: Kehn-Hall
authors.affiliation: Center for Applied Proteomics and Personalized Medicine, George Mason University, Manassas, VA, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Luchini
authors.affiliation: Center for Applied Proteomics and Personalized Medicine, George Mason University, Manassas, VA, USA.
authors.forename: Lance
authors.initials: L
authors.lastname: Liotta
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Bailey
authors.affiliation: George Washington Medical School, Washington DC, USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: United States Army Medical Research Institute for Infectious Diseases, Fredrick, MD, USA.
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA.
authors.forename: Ramin M
authors.initials: RM
authors.lastname: Hakami
authors.affiliation: National Center for Biodefense and Infectious Diseases, and the School of Systems Biology, George Mason University, Manassas, VA, USA. Electronic address: fkashanc@gmu.edu.
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
mesh_terms: D017209:Apoptosis; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012295:Rift Valley Fever / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D012296:Rift Valley fever virus / Q000502:physiology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D017361:Viral Nonstructural Proteins
keywords: Apoptosis; Liver cells; Reactive oxygen species; Rift Valley fever virus; p53; p65