SpringerLink
Log in

A critical role of interferon-induced protein IFP35 in the type I interferon response in cells induced by foot-and-mouth disease virus (FMDV) protein 2C

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Foot-and-mouth disease virus (FMDV) protein 2C is one of the most highly conserved viral proteins among the serotypes of FMDV. However, its effect on host cell response is not very clear. In our previous report, we showed that FMDV protein 2C interacts with cellular protein N-myc and STAT interactor (Nmi), inducing moderate apoptosis in cells. Here, we show that transfection of HEK293T cells with pEGFP-N1-2C or pEGFP-N1-Nmi induces activation of type I interferon promoters, leading to delayed vesicular stomatitis virus (VSV) growth. Using immunoprecipitation and confocal microscopy assays, we found that interferon-induced protein IFP35 interacts with Nmi. Knockdown of IFP35 expression by siRNA abolished pEGFP-N1-2C and pEGFP-N1-Nmi-induced activation of type I interferon promoters and restored VSV growth, suggesting that IFP35 plays a critical role in the type I interferon response induced by FMDV protein 2C. These findings may help to further understand cell responses to FMDV infection.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

FMDV:

Foot-and-mouth disease virus

IFP35:

Interferon-induced 35-kDa protein

Nmi:

N-myc and STAT interactor

RNAi:

RNA interference

References

  1. Grubman MJ, Baxt B (2004) Foot-and-mouth disease. Clin Microbiol Rev 17:465–493

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Saiz M, Nunez JI, Jimenez-Clavero MA, Baranowski E, Sobrino F (2002) Foot-and-mouth disease virus: biology and prospects for disease control. Microbes Infect 4:1183–1192

    Article  PubMed  Google Scholar 

  3. Gorbalenya AE, Koonin EV (1989) Viral proteins containing the purine NTP-binding sequence pattern. Nucleic Acids Res 17:8413–8440

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Echeverri A, Banerjee R, Dasgupta A (1998) Amino-terminal region of poliovirus 2C protein is sufficient for membrane binding. Virus Res 54:217–223

    Article  PubMed  CAS  Google Scholar 

  5. Banerjee R, Dasgupta A (2001) Interaction of picornavirus 2C polypeptide with the viral negative-strand RNA. J Gen Virol 82:2621–2627

    PubMed  CAS  Google Scholar 

  6. Rodriguez PL, Carrasco L (1995) Poliovirus protein 2C contains two regions involved in RNA binding activity. J Biol Chem 270:10105–10112

    Article  PubMed  CAS  Google Scholar 

  7. Rodriguez PL, Carrasco L (1993) Poliovirus protein 2C has ATPase and GTPase activities. J Biol Chem 268:8105–8110

    PubMed  CAS  Google Scholar 

  8. Pfister T, Jones KW, Wimmer E (2000) A cysteine-rich motif in poliovirus protein 2C(ATPase) is involved in RNA replication and binds zinc in vitro. J Virol 74:334–343

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Sweeney TR, Cisnetto V, Bose D, Bailey M, Wilson JR et al (2010) Foot-and-mouth disease virus 2C is a hexameric AAA + protein with a coordinated ATP hydrolysis mechanism. J Biol Chem 285:24347–24359

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Tang WF, Yang SY, Wu BW, Jheng JR, Chen YL et al (2007) Reticulon 3 binds the 2C protein of enterovirus 71 and is required for viral replication. J Biol Chem 282:5888–5898

    Article  PubMed  CAS  Google Scholar 

  11. Teterina NL, Gorbalenya AE, Egger D, Bienz K, Rinaudo MS et al (2006) Testing the modularity of the N-terminal amphipathic helix conserved in picornavirus 2C proteins and hepatitis C NS5A protein. Virology 344:453–467

    Article  PubMed  CAS  Google Scholar 

  12. Bienz K, Egger D, Troxler M, Pasamontes L (1990) Structural organization of poliovirus RNA replication is mediated by viral proteins of the P2 genomic region. J Virol 64:1156–1163

    PubMed  CAS  PubMed Central  Google Scholar 

  13. Moffat K, Howell G, Knox C, Belsham GJ, Monaghan P et al (2005) Effects of foot-and-mouth disease virus nonstructural proteins on the structure and function of the early secretory pathway: 2BC but not 3A blocks endoplasmic reticulum-to-Golgi transport. J Virol 79:4382–4395

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Moffat K, Knox C, Howell G, Clark SJ, Yang H et al (2007) Inhibition of the secretory pathway by foot-and-mouth disease virus 2BC protein is reproduced by coexpression of 2B with 2C, and the site of inhibition is determined by the subcellular location of 2C. J Virol 81:1129–1139

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Wang J, Wang Y, Liu J, Ding L, Zhang Q et al (2012) A critical role of N-myc and STAT interactor (Nmi) in foot-and-mouth disease virus (FMDV) 2C-induced apoptosis. Virus Res 170:59–65

    Article  PubMed  CAS  Google Scholar 

  16. Payvandi F, Amrute S, Fitzgerald-Bocarsly P (1998) Exogenous and endogenous IL-10 regulate IFN-alpha production by peripheral blood mononuclear cells in response to viral stimulation. J Immunol 160:5861–5868

    PubMed  CAS  Google Scholar 

  17. Sharma P, Kumar S, Kundu GC (2010) Transcriptional regulation of human osteopontin promoter by histone deacetylase inhibitor, trichostatin A in cervical cancer cells. Mol Cancer 9:178

    Article  PubMed  PubMed Central  Google Scholar 

  18. Palomares RA, Walz HG, Brock KV (2013) Expression of type I interferon-induced antiviral state and pro-apoptosis markers during experimental infection with low or high virulence bovine viral diarrhea virus in beef calves. Virus Res 173:260–269

    Article  PubMed  CAS  Google Scholar 

  19. Lechner J, Malloth N, Seppi T, Beer B, Jennings P et al (2008) IFN-alpha induces barrier destabilization and apoptosis in renal proximal tubular epithelium. Am J Physiol Cell Physiol 294:C153–C160

    Article  PubMed  CAS  Google Scholar 

  20. Thyrell L, Hjortsberg L, Arulampalam V, Panaretakis T, Uhles S et al (2004) Interferon alpha-induced apoptosis in tumor cells is mediated through the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway. J Biol Chem 279:24152–24162

    Article  PubMed  CAS  Google Scholar 

  21. Le Page C, Genin P, Baines MG, Hiscott J (2000) Interferon activation and innate immunity. Rev Immunogenet 2:374–386

    PubMed  Google Scholar 

  22. Li X, Wang J, Liu J, Li Z, Wang Y et al (2013) Engagement of soluble resistance-related calcium binding protein (sorcin) with foot-and-mouth disease virus (FMDV) VP1 inhibits type I interferon response in cells. Vet Microbiol 166:35–46

    Article  PubMed  CAS  Google Scholar 

  23. Hou F, Liu K, Shen T, Zhou B, Cao R et al (2011) Antiviral activity of rChIFN-alpha against vesicular stomatitis virus and Newcastle disease virus: a novel recombinant chicken interferon-alpha showed high antiviral activity. Res Vet Sci 91:e73–e79

    Article  PubMed  CAS  Google Scholar 

  24. Trottier MJ, Palian BM, Reiss CS (2005) VSV replication in neurons is inhibited by type I IFN at multiple stages of infection. Virology 333:215–225

    Article  PubMed  CAS  Google Scholar 

  25. Tan J, Qiao W, Wang J, Xu F, Li Y et al (2008) IFP35 is involved in the antiviral function of interferon by association with the viral tas transactivator of bovine foamy virus. J Virol 82:4275–4283

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Zhang L, Tang Y, Tie Y, Tian C, Wang J et al (2007) The PH domain containing protein CKIP-1 binds to IFP35 and Nmi and is involved in cytokine signaling. Cell Signal 19:932–944

    Article  PubMed  CAS  Google Scholar 

  27. Teterina NL, Gorbalenya AE, Egger D, Bienz K, Ehrenfeld E (1997) Poliovirus 2C protein determinants of membrane binding and rearrangements in mammalian cells. J Virol 71:8962–8972

    PubMed  CAS  PubMed Central  Google Scholar 

  28. Echeverri AC, Dasgupta A (1995) Amino terminal regions of poliovirus 2C protein mediate membrane binding. Virology 208:540–553

    Article  PubMed  CAS  Google Scholar 

  29. Schlegel A, Giddings TJ, Ladinsky MS, Kirkegaard K (1996) Cellular origin and ultrastructure of membranes induced during poliovirus infection. J Virol 70:6576–6588

    PubMed  CAS  PubMed Central  Google Scholar 

  30. Lippincott-Schwartz J (1993) Bidirectional membrane traffic between the endoplasmic reticulum and Golgi apparatus. Trends Cell Biol 3:81–88

    Article  PubMed  CAS  Google Scholar 

  31. Bange FC, Vogel U, Flohr T, Kiekenbeck M, Denecke B et al (1994) IFP 35 is an interferon-induced leucine zipper protein that undergoes interferon-regulated cellular redistribution. J Biol Chem 269:1091–1098

    PubMed  CAS  Google Scholar 

  32. Lee ND, Chen J, Shpall RL, Naumovski L (1999) Subcellular localization of interferon-inducible Myc/stat-interacting protein Nmi is regulated by a novel IFP 35 homologous domain. J Interferon Cytokine Res 19:1245–1252

    Article  PubMed  Google Scholar 

  33. Chen J, Shpall RL, Meyerdierks A, Hagemeier M, Bottger EC et al (2000) Interferon-inducible Myc/STAT-interacting protein Nmi associates with IFP 35 into a high molecular mass complex and inhibits proteasome-mediated degradation of IFP 35. J Biol Chem 275:36278–36284

    Article  PubMed  CAS  Google Scholar 

  34. Zhou X, Liao J, Meyerdierks A, Feng L, Naumovski L et al (2000) Interferon-alpha induces nmi-IFP35 heterodimeric complex formation that is affected by the phosphorylation of IFP35. J Biol Chem 275:21364–21371

    Article  PubMed  CAS  Google Scholar 

  35. Wang X, Johansen LM, Tae HJ, Taparowsky EJ (1996) IFP 35 forms complexes with B-ATF, a member of the AP1 family of transcription factors. Biochem Biophys Res Commun 229:316–322

    Article  PubMed  CAS  Google Scholar 

  36. Wang J, Yang B, Hu Y, Zheng Y, Zhou H et al (2013) Negative regulation of Nmi on virus-triggered type I IFN production by targeting IRF7. J Immunol 191:3393–3399

    Article  PubMed  CAS  Google Scholar 

  37. Das A, Dinh PX, Panda D, Pattnaik AK (2014) Interferon-inducible protein IFI35 negatively regulates RIG-I antiviral signaling and supports vesicular stomatitis virus replication. J Virol 88:3103–3113

    Article  PubMed  PubMed Central  Google Scholar 

  38. Han KJ, Su X, Xu LG, Bin LH, Zhang J et al (2004) Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. J Biol Chem 279:15652–15661

    Article  PubMed  CAS  Google Scholar 

  39. Yan Q, Carmody RJ, Qu Z, Ruan Q, Jager J et al (2012) Nuclear factor-kappaB binding motifs specify toll-like receptor-induced gene repression through an inducible repressosome. Proc Natl Acad Sci USA 109:14140–14145

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Fillmore RA, Mitra A, ** Y, Ju J, Scammell J et al (2009) Nmi (N-myc interactor) inhibits Wnt/beta-catenin signaling and retards tumor growth. Int J Cancer 125:556–564

    Article  PubMed  CAS  Google Scholar 

  41. Chinsangaram J, Piccone ME, Grubman MJ (1999) Ability of foot-and-mouth disease virus to form plaques in cell culture is associated with suppression of alpha/beta interferon. J Virol 73:9891–9898

    PubMed  CAS  PubMed Central  Google Scholar 

  42. de Los ST, de Avila BS, Weiblen R, Grubman MJ (2006) The leader proteinase of foot-and-mouth disease virus inhibits the induction of beta interferon mRNA and blocks the host innate immune response. J Virol 80:1906–1914

    Article  Google Scholar 

Download references

Acknowledgments

We thank Dr. Jue Liu for his generous assistance. This work was supported by grants from the National Natural Science Foundation of China (#31072117 to SJZ and 31272543 to SJZ)

Conflict of interest

The authors have declared that no conflict of interest exists.

Author information

Authors and Affiliations

  1. The Laboratory of Molecule and Cellular Physiology, School of Life Sciences, Northeast Normal University, Changchun, 130024, Jilin, China

    Wei Zheng & Qinghua Zeng

  2. State Key Laboratory of Agrobiotechnology, China Agricultural University, Bei**g, 100193, China

    Wei Zheng, **aying Li, Jianchang Wang, **aoqi Li, Hong Cao, Yongqiang Wang & Shijun J. Zheng

  3. Key Laboratory of Zoonosis of Ministry of Agriculture, China Agricultural University, Bei**g, 100193, China

    Wei Zheng, **aying Li, Jianchang Wang, **aoqi Li, Hong Cao, Yongqiang Wang & Shijun J. Zheng

  4. College of Veterinary Medicine, China Agricultural University, 2 Yuan-Ming-Yuan West Road, Bei**g, 100193, China

    Wei Zheng, **aying Li, Jianchang Wang, **aoqi Li, Hong Cao, Yongqiang Wang & Shijun J. Zheng

Authors
  1. Wei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. **aying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianchang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. **aoqi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yongqiang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qinghua Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shijun J. Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qinghua Zeng or Shijun J. Zheng.

Electronic supplementary material

Below is the link to the electronic supplementary material.

705_2014_2147_MOESM1_ESM.tif

Supplementary Fig. 1. Activation of IFN-α promoter by 2C, Nmi or 2C/Nmi. 293T cells (1 × 105) were transfected with the indicated expression plasmids (0.5 mg each) together with the indicated reporter plasmids (0.1 mg each) and the pRL-TK Renilla reporter plasmids (0.01 mg). Reporter assays were performed using a dual-specific luciferase assay kit at 6, 12 and 24 h after the transfection. (TIFF 280 kb)

705_2014_2147_MOESM2_ESM.tif

Supplementary Fig. 2. siRNA resistant form of IFP35 restored type I interferon response in IFP35 RNAi-treated cells. A. Gene sequence of IFP35. The domain targeted by siRNA is highlighted in red. B. Gene sequence of the RNAi-resistant form of IFP35. The siRNA targeting site in (A) was mutated and is highlighted in green. The RNAi resistant form of IFP35 was used to construct pEGFP-mutant vector. C. HEK293T cells were transfected with IFP35 RNAi plasmid or control vector. The IFP35 RNAi stable cell line was selected with puromycin (1 μg/mL in culture medium) and transfected with pEGFP-RNAi-resistant mutant IFP35 vector plus pEGFP empty vector, or pEGFP-N1-2C or pEGFP-N1-Nmi constructs. Twenty-four hours after transfection with pEGFP-N1-2C or pEGFP-N1-Nmi or empty vector as control together with 0.1 μg of IFN-α promoter gene plasmids and 0.01 μg of pRL-TK Renilla reporter plasmids, cells were collected, and the activity of the IFN-α promoter was measured by luciferase reporter gene assay using a dual-specific luciferase assay kit. Data are presented as mean +/- SD, n = 3. ** stands for p < 0.01 and * for p < 0.05. (TIFF 1074 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, W., Li, X., Wang, J. et al. A critical role of interferon-induced protein IFP35 in the type I interferon response in cells induced by foot-and-mouth disease virus (FMDV) protein 2C. Arch Virol 159, 2925–2935 (2014). https://doi.org/10.1007/s00705-014-2147-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-014-2147-7

Keywords

Search

Navigation