Skip to main content

Stress Granule Formation is One of the Early Antiviral Mechanisms for Host Cells Against Coxsackievirus B Infection

Virologica Sinica volume 33, pages 314–322 (2018)Cite this article

Abstract

Stress granules (SGs) are intracellular granules formed when cellular translation is blocked and have been reported to be involved in a variety of viral infections. Our previous studies revealed that SGs are involved in the coxsackievirus B (CVB) infection process, but the role of SGs in CVB infection has not been fully explored. In this study, we found that CVB type 3 (CVB3) could induce SG formation in the early phase of infection. Results showed that levels of CVB3 RNA and protein were significantly inhibited during the early stage of CVB3 infection by the elevated formation of SGs, while viral RNA and protein synthesis were significantly promoted when SG formation was blocked. Our findings suggest that SG formation is one of the early antiviral mechanisms for host cells against CVB infection.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  • Amorim R, Temzi A, Griffin BD, Mouland AJ (2017) Zika virus inhibits eIF2alpha-dependent stress granule assembly. PLoS Neglect Trop D 11:e0005775

    Article  Google Scholar 

  • Chapman NM, Ragland A, Leser JS, Hofling K, Willian S, Semler BL, Tracy S (2000) A group B coxsackievirus/poliovirus 5′ nontranslated region chimera can act as an attenuated vaccine strain in mice. J Virol 74:4047–4056

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chau DH, Yuan J, Zhang H, Cheung P, Lim T, Liu Z, Sall A, Yang D (2007) Coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through mitochondrial injury and cleavage of eIF4GI but not DAP5/p97/NAT1. Apoptosis 12:513–524

    Article  PubMed  CAS  Google Scholar 

  • Choudhury P, Bussiere L, Miller CL (2017) Mammalian orthoreovirus factories modulate stress granule protein localization by interaction with G3BP1. J Virol 91:e01298–e01317

    Article  PubMed Central  CAS  Google Scholar 

  • Dougherty JD, White JP, Lloyd RE (2011) Poliovirus-mediated disruption of cytoplasmic processing bodies. J Virol 85:64–75

    Article  PubMed  CAS  Google Scholar 

  • Dougherty JD, Tsai WC, Lloyd RE (2015) Multiple poliovirus proteins repress cytoplasmic RNA granules. Viruses 7:6127–6140

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fernandez-Carrillo C, Perez-Vilaro G, Diez J, Perez-Del-Pulgar S (2018) Hepatitis C virus plays with fire and yet avoids getting burned. A review for clinicians on processing bodies and stress granules. Liver Int 38:388–398

    Article  PubMed  Google Scholar 

  • Garaigorta U, Heim MH, Boyd B, Wieland S, Chisari FV (2012) Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress. J Virol 86:11043–11056

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Harkins S, Cornell CT, Whitton JL (2005) Analysis of translational initiation in coxsackievirus B3 suggests an alternative explanation for the high frequency of R+4 in the eukaryotic consensus motif. J Virol 79:987–996

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hashimoto S, Yamamoto S, Ogasawara N, Sato T, Yamamoto K, Katoh H, Kubota T, Shiraishi T, Kojima T, Himi T, Tsutsumi H, Yokota S (2016) Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production. PLoS ONE 11:e0161793

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kedersha N, Anderson P (2009) Regulation of translation by stress granules and processing bodies. Prog Mol Biol Transl 90:155–185

    CAS  Google Scholar 

  • Kedersha N, Tisdale S, Hickman T, Anderson P (2008) Real-time and quantitative imaging of mammalian stress granules and processing bodies. Method Enzymol 448:521–552

    Article  CAS  Google Scholar 

  • Kemball CC, Harkins S, Whitmire JK, Flynn CT, Feuer R, Whitton JL (2009) Coxsackievirus B3 inhibits antigen presentation in vivo, exerting a profound and selective effect on the MHC class I pathway. PLoS Pathog 5:e1000618

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lindquist ME, Lifland AW, Utley TJ, Santangelo PJ, Crowe JE Jr (2010) Respiratory syncytial virus induces host RNA stress granules to facilitate viral replication. J Virol 84:12274–12284

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lindquist ME, Mainou BA, Dermody TS, Crowe JE Jr (2011) Activation of protein kinase R is required for induction of stress granules by respiratory syncytial virus but dispensable for viral replication. Virology 413:103–110

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  • Lloyd RE (2013) Regulation of stress granules and P-bodies during RNA virus infection. RNA 4:317–331

    PubMed  CAS  Google Scholar 

  • Lloyd RE (2016) Enterovirus control of translation and RNA granule stress responses. Viruses 8:93

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Luo H, Yanagawa B, Zhang J, Luo Z, Zhang M, Esfandiarei M, Carthy C, Wilson JE, Yang D, McManus BM (2002) Coxsackievirus B3 replication is reduced by inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway. J Virol 76:3365–3373

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Miller CL (2011) Stress granules and virus replication. Future Virol 6:1329–1338

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mok BW, Song W, Wang P, Tai H, Chen Y, Zheng M, Wen X, Lau SY, Wu WL, Matsumoto K, Yuen KY, Chen H (2012) The NS1 protein of influenza A virus interacts with cellular processing bodies and stress granules through RNA-associated protein 55 (RAP55) during virus infection. J Virol 86:12695–12707

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Montero H, Trujillo-Alonso V (2011) Stress granules in the viral replication cycle. Viruses 3:2328–2338

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moutaoufik MT, El Fatimy R, Nassour H, Gareau C, Lang J, Tanguay RM, Mazroui R, Khandjian EW (2014) UVC-induced stress granules in mammalian cells. PLoS ONE 9:e112742

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pager CT, Schutz S, Abraham TM, Luo G, Sarnow P (2013) Modulation of hepatitis C virus RNA abundance and virus release by dispersion of processing bodies and enrichment of stress granules. Virology 435:472–484

    Article  PubMed  CAS  Google Scholar 

  • Palangi F, Samuel SM, Thompson IR, Triggle CR, Emara MM (2017) Effects of oxidative and thermal stresses on stress granule formation in human induced pluripotent stem cells. PLoS ONE 12:e0182059

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Panas MD, Varjak M, Lulla A, Eng KE, Merits A, Karlsson Hedestam GB, McInerney GM (2012) Sequestration of G3BP coupled with efficient translation inhibits stress granules in Semliki Forest virus infection. Mol Biol Cell 23:4701–4712

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Piotrowska J, Hansen SJ, Park N, Jamka K, Sarnow P, Gustin KE (2010) Stable formation of compositionally unique stress granules in virus-infected cells. J Virol 84:3654–3665

    Article  PubMed  CAS  Google Scholar 

  • Raaben M, Groot Koerkamp MJ, Rottier PJ, de Haan CA (2007) Mouse hepatitis coronavirus replication induces host translational shutoff and mRNA decay, with concomitant formation of stress granules and processing bodies. Cell Microbiol 9:2218–2229

    Article  PubMed  CAS  Google Scholar 

  • Rassmann A, Henke A, Zobawa M, Carlsohn M, Saluz HP, Grabley S, Lottspeich F, Munder T (2006) Proteome alterations in human host cells infected with coxsackievirus B3. J Gen Virol 87:2631–2638

    Article  PubMed  CAS  Google Scholar 

  • Slaine PD, Kleer M, Smith NK, Khaperskyy DA, McCormick C (2017) Stress granule-inducing eukaryotic translation initiation factor 4A inhibitors block influenza a virus replication. Viruses 9:E388

    Article  PubMed  Google Scholar 

  • White JP, Lloyd RE (2011) Poliovirus unlinks TIA1 aggregation and mRNA stress granule formation. J Virol 85:12442–12454

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • White JP, Lloyd RE (2012) Regulation of stress granules in virus systems. Trends Microbiol 20:175–183

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu S, Lin L, Zhao W, Li X, Wang Y, Si X, Wang T, Wu H, Zhai X, Zhong X, Gao S, Tong L, Xu Z, Zhong Z (2014a) AUF1 is recruited to the stress granules induced by coxsackievirus B3. Virus Res 192:52–61

    Article  PubMed  CAS  Google Scholar 

  • Wu S, Wang Y, Lin L, Si X, Wang T, Zhong X, Tong L, Luan Y, Chen Y, Li X, Zhang F, Zhao W, Zhong Z (2014b) Protease 2A induces stress granule formation during coxsackievirus B3 and enterovirus 71 infections. Virol J 11:192

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Natural Science Foundation of China (Grant 81571999 to Z Zhong; 81672007 to W Zhao; 81772188 to Y Wang, 31300144 to T Wang). We are grateful to the technical support from Heilongjiang Provincial Key Laboratory of Pathogens and Immunity and Heilongjiang Provincial Science and Technology Innovation Team in Higher Education Institutes for Infection and Immunity of Harbin Medical University.

Author information

Author notes

    Authors and Affiliations

    1. Department of Microbiology, Harbin Medical University, Harbin, 150081, China

      Xia Zhai, Shuo Wu, Lexun Lin, Tianying Wang, Xiaoyan Zhong, Yang Chen, Weizhen Xu, Lei Tong, Yan Wang & Zhaohua Zhong

    2. Department of Cell Biology, Harbin Medical University, Harbin, 150081, China

      Wenran Zhao

    Authors
    1. Xia Zhai
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Shuo Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Lexun Lin
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Tianying Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xiaoyan Zhong
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Yang Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Weizhen Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Lei Tong
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Yan Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Wenran Zhao
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Zhaohua Zhong
      View author publications

      You can also search for this author in PubMed Google Scholar

    Contributions

    ZZ designed and guided the study. XZ, SW, LL, TW, XZ, YC, and WX performed the experiments. LT and YW contributed in the collection and analysis of data. ZZ and WZ wrote the manuscript. All authors read and approved the final manuscript.

    Corresponding authors

    Correspondence to Wenran Zhao or Zhaohua Zhong.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Animal and Human Rights Statement

    This article does not contain any studies with human or animal subjects performed by any of the authors.

    Additional information

    Xia Zhai and Shuo Wu have contributed equally to this work.

    Rights and permissions

    Reprints and Permissions

    About this article

    Verify currency and authenticity via CrossMark

    Cite this article

    Zhai, X., Wu, S., Lin, L. et al. Stress Granule Formation is One of the Early Antiviral Mechanisms for Host Cells Against Coxsackievirus B Infection. Virol. Sin. 33, 314–322 (2018). https://doi.org/10.1007/s12250-018-0040-3

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12250-018-0040-3

    Keywords

    • Coxsackievirus B (CVB)
    • Stress granule (SG)
    • Viral replication