Abstract
Bluetongue virus (BTV) has been found to trigger autophagy to favor its replication, but the underlying mechanisms have not been clarified. Here, we show that cellular energy metabolism is involved in BTV-induced autophagy. Cellular ATP synthesis was impaired by BTV1 infection, causing metabolic stress, which was responsible for activation of autophagy, since the conversion of LC3 and aggregation of GFP-LC3 (autophagy markers) were suppressed when infection-caused energy depletion was reversed via MP (metabolic substrate) treatment. The reduced virus yields with MP further supported this view. Overall, our findings suggest that BTV1-induced disruption of cellular energy metabolism contributes to autophagy, and this provides new insights into BTV-host interactions.
References
Maclachlan NJ, Mayo CE (2013) Potential strategies for control of bluetongue, a globally emerging, Culicoides-transmitted viral disease of ruminant livestock and wildlife. Antiviral Res 99(2):79–90. doi:10.1016/j.antiviral.2013.04.021
Roy P (2008) Bluetongue virus: dissection of the polymerase complex. J Gen Virol 89(Pt 8):1789–1804. doi:10.1099/vir.0.2008/002089-0
Feng Y, Yang T, Xu Q, Sun E, Li J, Lv S, Wang H, Zhang Q, Zhang J, Wu D (2015) Detection, discrimination and quantitation of 22 bluetongue virus serotypes using real-time RT-PCR with TaqMan MGB probes. Arch Virol 160(9):2249–2258. doi:10.1007/s00705-015-2499-7
Roy P (2005) Bluetongue virus proteins and particles and their role in virus entry, assembly, and release. Adv Virus Res 64:69–123. doi:10.1016/s0065-3527(05)64004-3
Patel A, Roy P (2014) The molecular biology of Bluetongue virus replication. Virus Res 182:5–20. doi:10.1016/j.virusres.2013.12.017
Yorimitsu T, Klionsky DJ (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ 12(Suppl 2):1542–1552. doi:10.1038/sj.cdd.4401765
Skendros P, Mitroulis I (2012) Host cell autophagy in immune response to zoonotic infections. Clin Dev Immunol 2012:910525. doi:10.1155/2012/910525
Deretic V (2010) Autophagy in infection. Curr Opin Cell Biol 22(2):252–262. doi:10.1016/j.ceb.2009.12.009
Lv S, Xu Q, Sun E, Yang T, Li J, Feng Y, Zhang Q, Wang H, Zhang J, Wu D (2015) Autophagy activated by bluetongue virus infection plays a positive role in its replication. Viruses 7(8):4657–4675. doi:10.3390/v7082838
Allonso D, Andrade IS, Conde JN, Coelho DR, Rocha DC, da Silva ML, Ventura GT, Silva EM, Mohana-Borges R (2015) Dengue virus NS1 protein modulates cellular energy metabolism by increasing glyceraldehyde-3-phosphate dehydrogenase activity. J Virol 89(23):11871–11883. doi:10.1128/jvi.01342-15
Kuballa P, Nolte WM, Castoreno AB, Xavier RJ (2012) Autophagy and the immune system. Annu Rev Immunol 30:611–646. doi:10.1146/annurev-immunol-020711-074948
Levine B (2005) Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 120(2):159–162. doi:10.1016/j.cell.2005.01.005
El-Bacha T, Midlej V, Pereira da Silva AP, Silva da Costa L, Benchimol M, Galina A, Da Poian AT (2007) Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus. Biochim Biophys Acta 1772(10):1158–1166. doi:10.1016/j.bbadis.2007.08.003
Bhutia SK, Kegelman TP, Das SK, Azab B, Su ZZ, Lee SG, Sarkar D, Fisher PB (2010) Astrocyte elevated gene-1 induces protective autophagy. Proc Natl Acad Sci USA 107(51):22243–22248. doi:10.1073/pnas.1009479107
Barth S, Glick D, Macleod KF (2010) Autophagy: assays and artifacts. J Pathol 221(2):117–124. doi:10.1002/path.2694
Mizushima N (2004) Methods for monitoring autophagy. Int J Biochem Cell Biol 36(12):2491–2502. doi:10.1016/j.biocel.2004.02.005
Klionsky DJ, Abdelmohsen K, Abe A et al (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12(1):1–222. doi:10.1080/15548627.2015.1100356
Meley D, Bauvy C, Houben-Weerts JH, Dubbelhuis PF, Helmond MT, Codogno P, Meijer AJ (2006) AMP-activated protein kinase and the regulation of autophagic proteolysis. J Biol Chem 281(46):34870–34879. doi:10.1074/jbc.M605488200
Qi D, Young LH (2015) AMPK: energy sensor and survival mechanism in the ischemic heart. Trends Endocrinol Metab 26(8):422–429. doi:10.1016/j.tem.2015.05.010
Tait SW, Green DR (2012) Mitochondria and cell signalling. J Cell Sci 125(Pt 4):807–815. doi:10.1242/jcs.099234
Shang L, Wang X (2011) AMPK and mTOR coordinate the regulation of Ulk1 and mammalian autophagy initiation. Autophagy 7(8):924–926
Acknowledgments
This study was supported by grants from the National Natural Science Foundation of China (No. 31402207 and 31302065), Basic Scientific Research Foundation of Central Research Academies and Institutes (0302015008) and National High-Tech Research and Development Program of China (No. 2011AA10A212).
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Lv, S., Xu, Q., Sun, E. et al. Impaired cellular energy metabolism contributes to bluetongue-virus-induced autophagy. Arch Virol 161, 2807–2811 (2016). https://doi.org/10.1007/s00705-016-2924-6
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DOI: https://doi.org/10.1007/s00705-016-2924-6