West Nile Virus Growth is Independent of Autophagy Activation

Overview

Journal Virology

Specialty Microbiology

Date 2012 Sep 4

PMID 22939285

Citations 47

Authors

Erica Beatman

Ryan Oyer

Katherine D Shives

Karla Hedman

Aaron C Brault

Kenneth L Tyler

J David Beckham

Affiliations

Soon will be listed here.

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.

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References

Jackson W, Giddings Jr T, Taylor M, Mulinyawe S, Rabinovitch M, Kopito R . Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol. 2005; 3(5):e156. PMC: 1084330. DOI: 10.1371/journal.pbio.0030156. View

Florey O, Kim S, Sandoval C, Haynes C, Overholtzer M . Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes. Nat Cell Biol. 2011; 13(11):1335-43. PMC: 3223412. DOI: 10.1038/ncb2363. View

Liang X, Kleeman L, Jiang H, Gordon G, Goldman J, Berry G . Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol. 1998; 72(11):8586-96. PMC: 110269. DOI: 10.1128/JVI.72.11.8586-8596.1998. View

Deretic V . Autophagy in infection. Curr Opin Cell Biol. 2010; 22(2):252-62. PMC: 2866841. DOI: 10.1016/j.ceb.2009.12.009. View

Levine B, Kroemer G . Autophagy in the pathogenesis of disease. Cell. 2008; 132(1):27-42. PMC: 2696814. DOI: 10.1016/j.cell.2007.12.018. View

Mizushima N . The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol. 2010; 22(2):132-9. DOI: 10.1016/j.ceb.2009.12.004. View

Richardson-Burns S, Kominsky D, Tyler K . Reovirus-induced neuronal apoptosis is mediated by caspase 3 and is associated with the activation of death receptors. J Neurovirol. 2002; 8(5):365-80. DOI: 10.1080/13550280260422677. View

Kirkegaard K . Subversion of the cellular autophagy pathway by viruses. Curr Top Microbiol Immunol. 2009; 335:323-33. DOI: 10.1007/978-3-642-00302-8_16. View

Ke P, Chen S . Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J Clin Invest. 2010; 121(1):37-56. PMC: 3007134. DOI: 10.1172/JCI41474. View

10.

Kudchodkar S, Levine B . Viruses and autophagy. Rev Med Virol. 2009; 19(6):359-78. PMC: 2852112. DOI: 10.1002/rmv.630. View

11.

Talloczy Z, Virgin 4th H, Levine B . PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy. 2006; 2(1):24-9. DOI: 10.4161/auto.2176. View

12.

Dreux M, Gastaminza P, Wieland S, Chisari F . The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci U S A. 2009; 106(33):14046-51. PMC: 2729017. DOI: 10.1073/pnas.0907344106. View

13.

Brault A, Huang C, Langevin S, Kinney R, Bowen R, Ramey W . A single positively selected West Nile viral mutation confers increased virogenesis in American crows. Nat Genet. 2007; 39(9):1162-6. PMC: 2291521. DOI: 10.1038/ng2097. View

14.

Li J, Liang J, Liao C, Lin Y . Autophagy is involved in the early step of Japanese encephalitis virus infection. Microbes Infect. 2011; 14(2):159-68. DOI: 10.1016/j.micinf.2011.09.001. View

15.

Johansen T, Lamark T . Selective autophagy mediated by autophagic adapter proteins. Autophagy. 2010; 7(3):279-96. PMC: 3060413. DOI: 10.4161/auto.7.3.14487. View

16.

Taylor M, Kirkegaard K . Potential subversion of autophagosomal pathway by picornaviruses. Autophagy. 2007; 4(3):286-9. DOI: 10.4161/auto.5377. View

17.

McLean J, Wudzinska A, Datan E, Quaglino D, Zakeri Z . Flavivirus NS4A-induced autophagy protects cells against death and enhances virus replication. J Biol Chem. 2011; 286(25):22147-59. PMC: 3121359. DOI: 10.1074/jbc.M110.192500. View

18.

Klionsky D, Abeliovich H, Agostinis P, Agrawal D, Aliev G, Askew D . Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008; 4(2):151-75. PMC: 2654259. DOI: 10.4161/auto.5338. View

19.

Sanjuan M, Dillon C, Tait S, Moshiach S, Dorsey F, Connell S . Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature. 2007; 450(7173):1253-7. DOI: 10.1038/nature06421. View

20.

Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R . Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006; 441(7095):885-9. DOI: 10.1038/nature04724. View