TY - JOUR
T1 - Phosphoproteomic analysis reveals Smad protein family activation following Rift valley fever virus infection
AU - de la Fuente, Cynthia
AU - Pinkham, Chelsea
AU - Dabbagh, Deemah
AU - Beitzel, Brett
AU - Garrison, Aura
AU - Palacios, Gustavo
AU - Hodge, Kimberley Alex
AU - Petricoin, Emanuel F.
AU - Schmaljohn, Connie
AU - Campbell, Catherine E.
AU - Narayanan, Aarthi
AU - Kehn-Hall, Kylene
N1 - Publisher Copyright:
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2018/2
Y1 - 2018/2
N2 - Rift Valley fever virus (RVFV) infects both ruminants and humans leading to a wide variance of pathologies dependent on host background and age. Utilizing a targeted reverse phase protein array (RPPA) to define changes in signaling cascades after in vitro infection of human cells with virulent and attenuated RVFV strains, we observed high phosphorylation of Smad transcription factors. This evolutionarily conserved family is phosphorylated by and transduces the activation of TGF-β superfamily receptors. Moreover, we observed that phosphorylation of Smad proteins required active RVFV replication and loss of NSs impaired this activation, further corroborating the RPPA results. Gene promoter analysis of transcripts altered after RVFV infection identified 913 genes that contained a Smad-response element. Functional annotation of these potential Smad-regulated genes clustered in axonal guidance, hepatic fibrosis and cell signaling pathways involved in cellular adhesion/migration, calcium influx, and cytoskeletal reorganization. Furthermore, chromatin immunoprecipitation confirmed the presence of a Smad complex on the interleukin 1 receptor type 2 (IL1R2) promoter, which acts as a decoy receptor for IL-1 activation.
AB - Rift Valley fever virus (RVFV) infects both ruminants and humans leading to a wide variance of pathologies dependent on host background and age. Utilizing a targeted reverse phase protein array (RPPA) to define changes in signaling cascades after in vitro infection of human cells with virulent and attenuated RVFV strains, we observed high phosphorylation of Smad transcription factors. This evolutionarily conserved family is phosphorylated by and transduces the activation of TGF-β superfamily receptors. Moreover, we observed that phosphorylation of Smad proteins required active RVFV replication and loss of NSs impaired this activation, further corroborating the RPPA results. Gene promoter analysis of transcripts altered after RVFV infection identified 913 genes that contained a Smad-response element. Functional annotation of these potential Smad-regulated genes clustered in axonal guidance, hepatic fibrosis and cell signaling pathways involved in cellular adhesion/migration, calcium influx, and cytoskeletal reorganization. Furthermore, chromatin immunoprecipitation confirmed the presence of a Smad complex on the interleukin 1 receptor type 2 (IL1R2) promoter, which acts as a decoy receptor for IL-1 activation.
UR - http://www.scopus.com/inward/record.url?scp=85041660499&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0191983
DO - 10.1371/journal.pone.0191983
M3 - Article
C2 - 29408900
AN - SCOPUS:85041660499
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e0191983
ER -