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10.1016/j.virusres.2020.197961

http://scihub22266oqcxt.onion/10.1016/j.virusres.2020.197961
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32283129!7194644!32283129
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suck abstract from ncbi


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pmid32283129      Virus+Res 2020 ; 283 (ä): 197961
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  • Porcine deltacoronavirus activates the Raf/MEK/ERK pathway to promote its replication #MMPMID32283129
  • Jeon JH; Lee YJ; Lee C
  • Virus Res 2020[Jul]; 283 (ä): 197961 PMID32283129show ga
  • Porcine deltacoronavirus (PDCoV) is a newly emerged swine coronavirus that causes acute enteritis in neonatal piglets. To date, little is known about the host factors or cellular signaling mechanisms associated with PDCoV replication. Since the Raf/MEK/ERK pathway is involved in modulation of various important cellular functions, numerous DNA and RNA viruses coopt this pathway for efficient propagation. In the present study, we found that PDCoV induces the activation of ERK1/2 and its downstream substrate Elk-1 early in infection irrespective of viral biosynthesis. Chemical inhibition or knockdown of ERK1/2 significantly suppressed viral replication, whereas treatment with an ERK activator increased viral yields. Direct pharmacological inhibition of ERK activation had no effect on the viral entry process but sequentially affected the post-entry steps of the virus life cycle. In addition, pharmacological sequestration of cellular or viral cholesterol downregulated PDCoV-induced ERK signaling, highlighting the significance of the cholesterol contents in ERK activation. However, ERK inhibition had no effect on PDCoV-triggered apoptosis through activation of the cytochrome c-mediated intrinsic mitochondrial pathway, suggesting the irrelevance of ERK activation to the apoptosis pathway during PDCoV infection. Altogether, our findings indicate that the ERK signaling pathway plays a pivotal role in viral biosynthesis to facilitate the optimal replication of PDCoV.
  • |*Virus Replication[MESH]
  • |Active Transport, Cell Nucleus[MESH]
  • |Animals[MESH]
  • |Cell Nucleus/metabolism[MESH]
  • |Cells, Cultured[MESH]
  • |Cholesterol/metabolism[MESH]
  • |Coronavirus Infections/*metabolism/virology[MESH]
  • |Coronavirus/*physiology[MESH]
  • |Host-Pathogen Interactions[MESH]
  • |Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/genetics/*metabolism[MESH]
  • |Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/genetics/*metabolism[MESH]
  • |Phosphorylation[MESH]
  • |Signal Transduction[MESH]
  • |Swine[MESH]


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