title: West Nile virus growth is independent of autophagy activation.
abstract: West Nile virus (WNV) is an arthropod-borne virus with a worldwide distribution that causes neurologic disease and death. Autophagy is a cellular homeostatic mechanism involved in antiviral responses but can be subverted to support viral growth as well. We show that autophagy is induced by WNV infection in cell culture and in primary neuron cultures. Following WNV infection, lysosomes co-localize with autophagosomes resulting in LC3B-II turnover and autolysosomal acidification. However, activation or inhibition of autophagy has no significant effect on WNV growth but pharmacologic inhibition of PI3 kinases associated with autophagy reduce WNV growth. Basal levels of p62/sequestosome1(SQSTM1) do not significantly change following WNV-induced autophagy activation, but p62 is turned over or degraded by autophagy activation implying that p62 expression is increased following WNV-infection. These data show that WNV-induces autophagy but viral growth is independent of autophagy activation suggesting that WNV-specific interactions with autophagy have diverged from other flaviviruses.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Beatman
authors.forename: Ryan
authors.initials: R
authors.lastname: Oyer
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Shives
authors.forename: Karla
authors.initials: K
authors.lastname: Hedman
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Brault
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Tyler
authors.forename: J David
authors.initials: JD
authors.lastname: Beckham
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002522:Chlorocebus aethiops; D006224:Cricetinae; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D010588:Phagosomes / Q000378:metabolism / Q000821:virology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology*; D014902:West Nile virus / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008869:Microtubule-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors