Impaired Autophagy Flux is Associated with Proinflammatory Microglia Activation Following Japanese Encephalitis Virus Infection.
Autophagy
Japanese encephalitis virus infection
Microglia activation
Neuronal cell death
Journal
Neurochemical research
ISSN: 1573-6903
Titre abrégé: Neurochem Res
Pays: United States
ID NLM: 7613461
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
20
03
2020
accepted:
25
06
2020
revised:
05
05
2020
pubmed:
3
7
2020
medline:
9
6
2021
entrez:
3
7
2020
Statut:
ppublish
Résumé
Role of autophagy in Japanese encephalitis viral (JEV) infection is not well known. In the present study, we reported the role of autophagy flux in microglia activation, neurobehavioral function and neuronal death using a mouse model of JEV. Markers for autophagy (LC3-II/I, SQSTM1/P62, phos-Akt, phos-AMPK), and neuronal death (cleaved caspase 12, H2Ax, polyubiquitin) were investigated by western blot at 1, 3 and 7 days post inoculation. Cathepsin D was measured in cerebral cotex of JEV infected mice spectrophotometrically. Microglia activation and pro-inflammatory cytokines (IL1β, TNF-α, IFNγ, IL6) were measured by immunohistochemistry, western blot and qPCR analysis. In order to determine the neuroinflammatory changes and autophagy mediated neuronal cell death, BV2-microglia and N2a-neuronal cells were used. Autophagy activation marker LC3-II/I and its substrate SQSTM1/P62 were significantly increased while cathepsin D activity was decreased on day 7 post inoculation in cerebral cortex. Microglia in cortex were activated and showed higher expression of proinflammatory mRNA of IL1β, TNF-α, IFNγ and IL6, with increased DNA damage (H2AX) and neuronal cell death pathways in hippocampus and neurobehavioral dysfunction. Similar observations on JEV infection mediated autophagy flux inhibition and neuronal cell death was found in N2a neuronal cell. Collectively, our study provides evidence on the role of autophagy regulation, microglial activation and neurodegeneration following JEV infection.
Identifiants
pubmed: 32613347
doi: 10.1007/s11064-020-03080-5
pii: 10.1007/s11064-020-03080-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2184-2195Subventions
Organisme : Department of Biotechnology, Government of West Bengal
ID : BT/RLF/Re-entry/13/2014
Références
Ke PY (2018) The multifaceted roles of autophagy in flavivirus-host interactions. Int J Mol Sci 19(12):3940. https://doi.org/10.3390/ijms19123940
doi: 10.3390/ijms19123940
pmcid: 6321027
Sharma M, Sharma KB, Chauhan S, Bhattacharyya S, Vrati S, Kalia M (2018) Diphenyleneiodonium enhances oxidative stress and inhibits Japanese encephalitis virus induced autophagy and ER stress pathways. Biochem Biophys Res Commun 502(2):232–237. https://doi.org/10.1016/j.bbrc.2018.05.149
doi: 10.1016/j.bbrc.2018.05.149
pubmed: 29792860
Jin R, Zhu W, Cao S, Chen R, Jin H, Liu Y, Wang S, Wang W, Xiao G (2013) Japanese encephalitis virus activates autophagy as a viral immune evasion strategy. PLoS ONE 8(1):e52909. https://doi.org/10.1371/journal.pone.0052909
doi: 10.1371/journal.pone.0052909
pubmed: 23320079
pmcid: 3540057
Lee YR, Lei HY, Liu MT, Wang JR, Chen SH, Jiang-Shieh YF, Lin YS, Yeh TM, Liu CC, Liu HS (2008) Autophagic machinery activated by dengue virus enhances virus replication. Virology 374(2):240–248. https://doi.org/10.1016/j.virol.2008.02.016
doi: 10.1016/j.virol.2008.02.016
pubmed: 18353420
pmcid: 7103294
Sir D, Chen WL, Choi J, Wakita T, Yen TS, Ou JH (2008) Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response. Hepatology 48(4):1054–1061. https://doi.org/10.1002/hep.22464
doi: 10.1002/hep.22464
pubmed: 18688877
pmcid: 2562598
Li JK, Liang JJ, Liao CL, Lin YL (2012) Autophagy is involved in the early step of Japanese encephalitis virus infection. Microbes Infect 14(2):159–168. https://doi.org/10.1016/j.micinf.2011.09.001
doi: 10.1016/j.micinf.2011.09.001
pubmed: 21946213
Ghoshal A, Das S, Ghosh S, Mishra MK, Sharma V, Koli P, Sen E, Basu A (2007) Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis. Glia 55(5):483–496. https://doi.org/10.1002/glia.20474
doi: 10.1002/glia.20474
pubmed: 17203475
Kalita J, Misra UK (2000) Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis. J Neurol Sci 174(1):3–8
doi: 10.1016/S0022-510X(99)00318-4
Saxena V, Mathur A, Krishnani N, Dhole TN (2008) An insufficient anti-inflammatory cytokine response in mouse brain is associated with increased tissue pathology and viral load during Japanese encephalitis virus infection. Arch Virol 153(2):283–292. https://doi.org/10.1007/s00705-007-1098-7
doi: 10.1007/s00705-007-1098-7
pubmed: 18074098
Bodea LG, Wang Y, Linnartz-Gerlach B, Kopatz J, Sinkkonen L, Musgrove R, Kaoma T, Muller A, Vallar L, Di Monte DA, Balling R, Neumann H (2014) Neurodegeneration by activation of the microglial complement-phagosome pathway. J Neurosci 34(25):8546–8556. https://doi.org/10.1523/JNEUROSCI.5002-13.2014
doi: 10.1523/JNEUROSCI.5002-13.2014
pubmed: 24948809
pmcid: 6608212
Das S, Basu A (2008) Japanese encephalitis virus infects neural progenitor cells and decreases their proliferation. J Neurochem 106(4):1624–1636. https://doi.org/10.1111/j.1471-4159.2008.05511.x
doi: 10.1111/j.1471-4159.2008.05511.x
pubmed: 18540995
Mukherjee S, Singh N, Sengupta N, Fatima M, Seth P, Mahadevan A, Shankar SK, Bhattacharyya A, Basu A (2017) Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress. Cell Death Dis 8(1):e2556. https://doi.org/10.1038/cddis.2016.394
doi: 10.1038/cddis.2016.394
pubmed: 28102850
pmcid: 5386351
Sharma M, Bhattacharyya S, Nain M, Kaur M, Sood V, Gupta V, Khasa R, Abdin MZ, Vrati S, Kalia M (2014) Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes. Autophagy 10(9):1637–1651. https://doi.org/10.4161/auto.29455
doi: 10.4161/auto.29455
pubmed: 25046112
pmcid: 4206540
Shukla V, Shakya AK, Shukla M, Kumari N, Krishnani N, Dhole TN, Misra UK (2016) Circulating levels of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases during Japanese encephalitis virus infection. Virusdisease 27(1):63–76. https://doi.org/10.1007/s13337-015-0301-9
doi: 10.1007/s13337-015-0301-9
pubmed: 26925446
pmcid: 4758310
Yang KD, Yeh WT, Chen RF, Chuon HL, Tsai HP, Yao CW, Shaio MF (2004) A model to study neurotropism and persistency of Japanese encephalitis virus infection in human neuroblastoma cells and leukocytes. J Gen Virol 85(Pt 3):635–642. https://doi.org/10.1099/vir.0.19426-0
doi: 10.1099/vir.0.19426-0
pubmed: 14993648
Kumar A, Barrett JP, Alvarez-Croda DM, Stoica BA, Faden AI, Loane DJ (2016) NOX2 drives M1-like microglial/macrophage activation and neurodegeneration following experimental traumatic brain injury. Brain Behav Immun 58:291–309. https://doi.org/10.1016/j.bbi.2016.07.158
doi: 10.1016/j.bbi.2016.07.158
pubmed: 27477920
pmcid: 5067217
Kyei GB, Dinkins C, Davis AS, Roberts E, Singh SB, Dong C, Wu L, Kominami E, Ueno T, Yamamoto A, Federico M, Panganiban A, Vergne I, Deretic V (2009) Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol 186(2):255–268. https://doi.org/10.1083/jcb.200903070
doi: 10.1083/jcb.200903070
pubmed: 19635843
pmcid: 2717652
Ding B, Zhang G, Yang X, Zhang S, Chen L, Yan Q, Xu M, Banerjee AK, Chen M (2014) Phosphoprotein of human parainfluenza virus type 3 blocks autophagosome-lysosome fusion to increase virus production. Cell Host Microbe 15(5):564–577. https://doi.org/10.1016/j.chom.2014.04.004
doi: 10.1016/j.chom.2014.04.004
pubmed: 24832451
Faure M (2014) The p value of HPIV3-mediated autophagy inhibition. Cell Host Microbe 15(5):519–521. https://doi.org/10.1016/j.chom.2014.04.014
doi: 10.1016/j.chom.2014.04.014
pubmed: 24832445
Chauhan PS, Khanna VK, Kalita J, Misra UK (2017) Japanese Encephalitis virus infection results in transient dysfunction of memory learning and cholinesterase inhibition. Mol Neurobiol 54(6):4705–4715. https://doi.org/10.1007/s12035-016-9963-6
doi: 10.1007/s12035-016-9963-6
pubmed: 27447805
Kalita J, Misra UK, Srivastava A (2009) Cognitive impairment in encephalitis: P3 and MRI correlation. Electromyogr Clin Neurophysiol 49(1):27–33
pubmed: 19280797
Misra UK, Kalita J (1997) Anterior horn cells are also involved in Japanese encephalitis. Acta Neurol Scand 96(2):114–117
doi: 10.1111/j.1600-0404.1997.tb00250.x
Bjorkoy G, Lamark T, Johansen T (2006) p62/SQSTM1: a missing link between protein aggregates and the autophagy machinery. Autophagy 2(2):138–139. https://doi.org/10.4161/auto.2.2.2405
doi: 10.4161/auto.2.2.2405
pubmed: 16874037
Ichimura Y, Kominami E, Tanaka K, Komatsu M (2008) Selective turnover of p62/A170/SQSTM1 by autophagy. Autophagy 4(8):1063–1066. https://doi.org/10.4161/auto.6826
doi: 10.4161/auto.6826
pubmed: 18776737
Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H, Johansen T (2005) p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 171(4):603–614. https://doi.org/10.1083/jcb.200507002
doi: 10.1083/jcb.200507002
pubmed: 16286508
pmcid: 2171557
Zhou J, Sinha RA, Lesmana R, Yau WWY, Yen PM (2018) Pharmacological inhibition of lysosomal activity as a method for monitoring thyroid hormone-induced autophagic flux in mammalian cells in vitro. Methods Mol Biol 1801:111–122. https://doi.org/10.1007/978-1-4939-7902-8_11
doi: 10.1007/978-1-4939-7902-8_11
pubmed: 29892821
pmcid: 6020991
Kumar A, Loane DJ (2012) Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behav Immun 26(8):1191–1201. https://doi.org/10.1016/j.bbi.2012.06.008
doi: 10.1016/j.bbi.2012.06.008
pubmed: 22728326
Kaushik DK, Gupta M, Kumawat KL, Basu A (2012) NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese encephalitis. PLoS ONE 7(2):e32270. https://doi.org/10.1371/journal.pone.0032270
doi: 10.1371/journal.pone.0032270
pubmed: 22393394
pmcid: 3290554
Silva AR, Santos AC, Farfel JM, Grinberg LT, Ferretti RE, Campos AH, Cunha IW, Begnami MD, Rocha RM, Carraro DM, de Braganca Pereira CA, Jacob-Filho W, Brentani H (2014) Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer’s disease. PLoS ONE 9(6):e99897. https://doi.org/10.1371/journal.pone.0099897
doi: 10.1371/journal.pone.0099897
pubmed: 24936870
pmcid: 4061071
Sips GJ, Wilschut J, Smit JM (2012) Neuroinvasive flavivirus infections. Rev Med Virol 22(2):69–87. https://doi.org/10.1002/rmv.712
doi: 10.1002/rmv.712
pubmed: 22086854
Yang S, Qiang L, Sample A, Shah P, He YY (2017) NF-kappaB signaling activation induced by chloroquine requires autophagosome, p62 protein, and c-Jun N-terminal kinase (JNK) signaling and promotes tumor cell resistance. J Biol Chem 292(8):3379–3388. https://doi.org/10.1074/jbc.M116.756536
doi: 10.1074/jbc.M116.756536
pubmed: 28082672
pmcid: 5336170
Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82(2):373–428. https://doi.org/10.1152/physrev.00027.2001
doi: 10.1152/physrev.00027.2001
pubmed: 11917093
Choy MM, Zhang SL, Costa VV, Tan HC, Horrevorts S, Ooi EE (2015) Proteasome inhibition suppresses dengue virus egress in antibody dependent infection. PLoS Negl Trop Dis 9(11):e0004058. https://doi.org/10.1371/journal.pntd.0004058
doi: 10.1371/journal.pntd.0004058
pubmed: 26565697
pmcid: 4643959
Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F, Montgomery RR, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H, Fikrig E (2008) RNA interference screen for human genes associated with West Nile virus infection. Nature 455(7210):242–245. https://doi.org/10.1038/nature07207
doi: 10.1038/nature07207
pubmed: 18690214
pmcid: 3136529
Wang S, Liu H, Zu X, Liu Y, Chen L, Zhu X, Zhang L, Zhou Z, Xiao G, Wang W (2016) The ubiquitin-proteasome system is essential for the productive entry of Japanese encephalitis virus. Virology 498:116–127. https://doi.org/10.1016/j.virol.2016.08.013
doi: 10.1016/j.virol.2016.08.013
pubmed: 27567260
Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501. https://doi.org/10.1038/nrc839nrc839[pii]
doi: 10.1038/nrc839nrc839[pii]
pubmed: 12094235
Hopkins TA, Dyck JR, Lopaschuk GD (2003) AMP-activated protein kinase regulation of fatty acid oxidation in the ischaemic heart. Biochem Soc Trans 31(Pt 1):207–212. https://doi.org/10.1042/bst0310207
doi: 10.1042/bst0310207
pubmed: 12546686