RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection of Intestinal Epithelial Cells.

Journal Article (Journal Article)

Receptor interacting protein kinase-3 (RIP3) is an essential kinase for necroptotic cell death signaling and has been implicated in antiviral cell death signaling upon DNA virus infection. Here, we performed high-throughput RNAi screening and identified RIP3 as a positive regulator of coxsackievirus B3 (CVB) replication in intestinal epithelial cells (IECs). RIP3 regulates autophagy, a process utilized by CVB for viral replication factory assembly, and depletion of RIP3 inhibits autophagic flux and leads to the accumulation of autophagosomes and amphisomes. Additionally, later in infection, RIP3 is cleaved by the CVB-encoded cysteine protease 3C(pro), which serves to abrogate RIP3-mediated necrotic signaling and induce a nonnecrotic form of cell death. Taken together, our results show that temporal targeting of RIP3 allows CVB to benefit from its roles in regulating autophagy while inhibiting the induction of necroptotic cell death.

Full Text

Duke Authors

Cited Authors

  • Harris, KG; Morosky, SA; Drummond, CG; Patel, M; Kim, C; Stolz, DB; Bergelson, JM; Cherry, S; Coyne, CB

Published Date

  • August 12, 2015

Published In

Volume / Issue

  • 18 / 2

Start / End Page

  • 221 - 232

PubMed ID

  • 26269957

Pubmed Central ID

  • PMC4562276

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2015.07.007


  • eng

Conference Location

  • United States