title: West Nile virus (WNV) replication is independent of autophagy in mammalian cells.
abstract: Autophagy is a homeostatic process responsible for recycling cytosolic proteins and organelles. Moreover, this pathway contributes to the cell's intrinsic innate defenses. While many viruses have evolved mechanisms to antagonize the antiviral effects of the autophagy pathway, others subvert autophagy to facilitate replication. Here, we have investigated the role of autophagy in West Nile virus (WNV) replication. Experiments in cell lines derived from a variety of sources, including the kidney, liver, skin, and brain, indicated that WNV replication does not upregulate the autophagy pathway. Furthermore, WNV infection did not inhibit rapamycin-induced autophagy, suggesting that WNV does not disrupt the authophagy signaling cascade. Perturbation of the autophagy pathway by depletion of the major autophagy factors Atg5 or Atg7 had no effect on WNV infectious particle production, indicating that WNV does not require a functional autophagy pathway for replication. Taken together, the results of our study provide evidence that WNV, unlike several other viruses of the family Flaviviridae, does not significantly interact with the conventional autophagy pathway in mammalian cells.
authors.affiliation: Department of Cell Biology and Molecular Genetics University of Maryland, College Park, MD, USA.
authors.forename: Rianna
authors.initials: R
authors.lastname: Vandergaast
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Fredericksen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology / Q000821:virology; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology / Q000821:virology; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D034622:RNA Interference; D000071456:Sequestosome-1 Protein; D012845:Sindbis Virus / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication; D014902:West Nile virus / Q000502:physiology*
chemical_list: C502778:ATG5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000071187:Autophagy-Related Protein 5; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein