Skip to main content
SpringerLink
Log in

Bovine viral diarrhea virus infection induces autophagy in MDBK cells

  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Bovine viral diarrhea virus (BVDV) is an enveloped, positive-sense, single-stranded RNA virus that belongs to the genus Pestivirus (Flaviviridae). The signaling pathways and levels of signaling molecules are altered in Madin-Darby Bovine Kidney (MDBK) cells infected with BVDV. Autophagy is a conservative biological degradation pathway that mainly eliminates and degrades damaged or superfluous organelles and macromolecular complexes for intracellular recycling in eukaryotic cells. Autophagy can also be induced as an effective response to maintain cellular homeostasis in response to different stresses, such as nutrient or growth factor deprivation, hypoxia, reactive oxygen species exposure and pathogen infection. However, the effects of BVDV infection on autophagy inMDBK cells remain unclear. Therefore, we performed an analysis of autophagic activity after BVDV NADL infection using real-time PCR, electron microscopy, laser confocal microscopy, and Western blotting analysis. The results demonstrated that BVDV NADL infection increased autophagic activity and significantly elevated the expression levels of the autophagy-related genes Beclin1 and ATG14 inMDBK cells. However, the knockdown of Beclin1 and ATG14 by RNA interference (RNAi) did not affect BVDV NADL infection-related autophagic activity. These findings provided a novel perspective to elaborate the effects of viral infection on the host cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Refrerences

  • Ashford, T.P. and Porter, K.R. 1962. Cytoplasmic components in hepatic cell lysosomes. J. Cell Biol. 12, 198–202.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Carpenter, J.E., Jackson, W., Benetti, L., and Grose, C. 2011. Autophagosome formation during varicella-zoster virus infection following endoplasmic reticulum stress and the unfolded protein response. J. Virol. 85, 9414–9424.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Deretic, V. 2006. Autophagy as an immune defense mechanism. Curr. Opin. Immunol. 18, 375–382.

    Article  CAS  PubMed  Google Scholar 

  • Dreux, M. and Chisari, F.V. 2010. Viruses and the autophagy machinery. Cell Cycle 9, 1295–1307.

    Article  CAS  PubMed  Google Scholar 

  • Dreux, M., Gastaminza, P., Wieland, S.F., and Chisari, F.V. 2009. The autophagy machinery is required to initiate hepatitis C virus replication. Proc. Natl. Acad. Sci. USA 106, 14046–14051.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ferdous, A., Battiprolu, P.K., Ni, Y.G., Rothermel, B.A., and Hill, J.A. 2010. FoxO, autophagy, and cardiac remodeling. J. Cardiovasc. Transl. Res. 3, 355–364.

    Article  PubMed Central  PubMed  Google Scholar 

  • Gangodkar, S., Jain, P., Dixit, N., Ghosh, K., and Basu, A. 2010. Dengue virus-induced autophagosomes and changes in endomembrane ultrastructure imaged by electron tomography and whole-mount grid-cell culture techniques. J. Electron Microsc. 59, 503–511.

    Article  Google Scholar 

  • Guo, F., Zhang, H., Chen, C., Hu, S., Wang, Y., Qiao, J., Ren, Y., Zhang, K., Wang, Y., and Du, G. 2012. Autophagy favors Brucella melitensis survival in infected macrophages. Cell Mol. Biol. Lett. 17, 249–257.

    Article  CAS  PubMed  Google Scholar 

  • He, C. and Klionsky, D.J. 2009. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet. 43, 67–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Heaton, N.S. and Randall, G. 2010. Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe 8, 422–432.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Heaton, N.S. and Randall, G. 2011. Dengue virus and autophagy. Viruses 3, 1332–1341.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Huang, H., Kang, R., Wang, J., Luo, G., Yang, W., and Zhao, Z. 2012. Hepatitis C virus inhibits AKT-tuberous sclerosis complex (TSC), the mechanistic target of rapamycin (mTOR) pathway, through endoplasmic reticulum stress to induce autophagy. Autophagy 9, 175–195.

    Article  PubMed  Google Scholar 

  • Hulst, M.M., van Gennip, H.G., and Moormann, R.J. 2000. Passage of classical swine fever virus in cultured swine kidney cells selects virus variants that bind to heparan sulfate due to a single amino acid change in envelope protein Erns. J. Virol. 74, 9553–9561.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kadowaki, M. and Karim, M.R. 2009. Cytosolic LC3 ratio as a quantitative index of macroautophagy. Methods Enzymol. 452, 199–213.

    Article  CAS  PubMed  Google Scholar 

  • Kang, R., Zeh, H.J., Lotze, M.T., and Tang, D. 2011. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 18, 571–580.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ke, P.Y. and Chen, S.S.L. 2011a. Autophagy: a novel guardian of HCV against innate immune response. Autophagy 7, 533–535.

    Article  PubMed  Google Scholar 

  • Ke, P.Y. and Chen, S.S.L. 2011b. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J. Clin. Invest. 121, 37.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Klionsky, D.J. 2007. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat. Rev. Mol. Cell Biol. 8, 931–937.

    Article  CAS  PubMed  Google Scholar 

  • Klionsky, D.J., Abdalla, F.C., Abeliovich, H., Abraham, R.T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., and Aguirre-Ghiso, J.A. 2012. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8, 445–544.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee, Y.R., Lei, H.Y., Liu, M.T., Wang, J.R., Chen, S.H., Jiang-Shieh, Y.F., Lin, Y.S., Yeh, T.M., Liu, C.C., and Liu, H.S. 2008. Autophagic machinery activated by dengue virus enhances virus replication. Virology 374, 240–248.

    Article  CAS  PubMed  Google Scholar 

  • Li, M., Jiang, X., Liu, D., Na, Y., Gao, G.F., and Xi, Z. 2008. Autophagy protects lncap cells under androgen deprivation conditions. Autophagy 4, 54–60.

    CAS  PubMed  Google Scholar 

  • Li, J., Liu, Y., Wang, Z., Liu, K., Wang, Y., Liu, J., Ding, H., and Yuan, Z. 2011. Subversion of cellular autophagy machinery by hepatitis B virus for viral envelopment. J. Virol. 85, 6319–6333.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Livak, K.J. and Schmittgen, T.D. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods 25, 402–408.

    Article  CAS  PubMed  Google Scholar 

  • Mateo, R., Nagamine, C.M., Spagnolo, J., Méndez, E., Rahe, M., Gale, M., Yuan, J., and Kirkegaard, K. 2013. Inhibition of cellular autophagy deranges dengue virion maturation. J. Virol. 87, 1312–1321.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mehrpour, M., Esclatine, A., Beau, I., and Codogno, P. 2010. Overview of macroautophagy regulation in mammalian cells. Cell Res. 20, 748–762.

    Article  PubMed  Google Scholar 

  • Mendez, E., Ruggli, N., Collett, M.S., and Rice, C.M. 1998. Infectious bovine viral diarrhea virus (strain NADL) RNA from stable cDNA clones: a cellular insert determines NS3 production and viral cytopathogenicity. J. Virol. 72, 4737–4745.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Meyers, G., Stoll, D., and Gunn, M. 1998. Insertion of a sequence encoding light chain 3 of microtubule-associated proteins 1A and 1B in a pestivirus genome: connection with virus cytopathogenicity and induction of lethal disease in cattle. J. Virol. 72, 4139–4148.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mizui, T., Yamashina, S., Tanida, I., Takei, Y., Ueno, T., Sakamoto, N., Ikejima, K., Kitamura, T., Enomoto, N., and Sakai, T. 2010. Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. J. Gastroenterol. 45, 195–203.

    Article  CAS  PubMed  Google Scholar 

  • Mizushima, N. 2007. Autophagy: process and function. Genes Dev. 21, 2861–2873.

    Article  CAS  PubMed  Google Scholar 

  • Mizushima, N., Levine, B., Cuervo, A.M., and Klionsky, D.J. 2008. Autophagy fights disease through cellular self-digestion. Nature 451, 1069–1075.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Obara, K. and Ohsumi, Y. 2011. Atg14: a key player in orchestrating autophagy. Int. J. Cell Biol. 2011, 71345.

    Article  Google Scholar 

  • Orvedahl, A., MacPherson, S., Sumpter Jr., R., Talloczy, Z., Zou, Z., and Levine, B. 2010. Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe 7, 115–127.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Perdrizet, J.A., Rebhun, W.C., Dubovi, E.J., and Donis, R.O. 1987. Bovine virus diarrhea-clinical syndromes in dairy herds. Cornell. Vet. 77, 46–74.

    CAS  PubMed  Google Scholar 

  • Reed, L.J. and Muench, H. 1938. A simple method of estimating fifty percent endpoints. Am. J. Epidemiol. 27, 493–497.

    Google Scholar 

  • Ridpath, J.F., Bolin, S.R., and Dubovi, E.J. 1994. Segregation of bovine viral diarrhea virus into genotypes. Virology 205, 66–74.

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Rocha, H., Gomez-Gutierrez, J.G., Garcia-Garcia, A., Rao, X.M., Chen, L., McMasters, K.M., and Zhou, H.S. 2011. Adenoviruses induce autophagy to promote virus replication and oncolysis. Virology 416, 9–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sir, D., Kuo, C.-f., Tian, Y., Liu, H.M., Huang, E.J., Jung, J.U., Machida, K., and Ou, J.-h.J. 2012. Replication of hepatitis C virus RNA on autophagosomal membranes. J. Biol. Chem. 287, 18036–18043.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tanida, I., Ueno, T., and Kominami, E. 2008. LC3 and autophagy. Methods Mol. Biol. 445, 77–88.

    Article  CAS  PubMed  Google Scholar 

  • Wong, J., Zhang, J., Si, X., Gao, G., Mao, I., McManus, B.M., and Luo, H. 2008. Autophagosome supports coxsackievirus B3 replication in host cells. J. Virol. 82, 9143–9153.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Xi, X., Zhang, X., Wang, B., Wang, T., Wang, J., Huang, H., Wang, J., Jin, Q., and Zhao, Z. 2013. The interplays between autophagy and apoptosis induced by enterovirus 71. PLoS ONE 8, e56966.

    Google Scholar 

  • Zhang, Y., Li, Z., Ge, X., Guo, X., and Yang, H. 2011. Autophagy promotes the replication of encephalomyocarditis virus in host cells. Autophagy 7, 613–628.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, Z., Fux, B., Goodwin, M., Dunay, I.R., Strong, D., Miller, B.C., Cadwell, K., Delgado, M.A., Ponpuak, M., Green, K.G., and et al. 2008. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Cell Host Microbe 4, 458–469.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang, 832003, P.R. China

    Qiang Fu, Huijun Shi, Jun Qiao, Pengyan Wang, Hui Zhang & Chuangfu Chen

  2. College of Medicine, Shihezi University, Shihezi, Xinjiang, 832003, P.R. China

    Yan Ren & Fei Guo

  3. College of Life Science, Shihezi University, Shihezi, Xinjiang, 832003, P.R. China

    Wei Ni

Authors
  1. Qiang Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huijun Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fei Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pengyan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chuangfu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chuangfu Chen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, Q., Shi, H., Ren, Y. et al. Bovine viral diarrhea virus infection induces autophagy in MDBK cells. J Microbiol. 52, 619–625 (2014). https://doi.org/10.1007/s12275-014-3479-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-014-3479-4

Keywords

Search

Navigation