title: p53 Activation following Rift Valley fever virus infection contributes to cell death and viral production.
abstract: Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production.
authors.affiliation: National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, United States of America.
authors.forename: Dana
authors.initials: D
authors.lastname: Austin
authors.forename: Alan
authors.initials: A
authors.lastname: Baer
authors.forename: Lindsay
authors.initials: L
authors.lastname: Lundberg
authors.forename: Nazly
authors.initials: N
authors.lastname: Shafagati
authors.forename: Annalise
authors.initials: A
authors.lastname: Schoonmaker
authors.forename: Aarthi
authors.initials: A
authors.lastname: Narayanan
authors.forename: Taissia
authors.initials: T
authors.lastname: Popova
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Panthier
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
authors.forename: Charles
authors.initials: C
authors.lastname: Bailey
authors.forename: Kylene
authors.initials: K
authors.lastname: Kehn-Hall
mesh_terms: D021581:Active Transport, Cell Nucleus; D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D012296:Rift Valley fever virus / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D016159:Tumor Suppressor Protein p53; D017361:Viral Nonstructural Proteins