SpringerLink
Log in

Porcine FcεRI Mediates Porcine Reproductive and Respiratory Syndrome Virus Multiplication and Regulates the Inflammatory Reaction

  • Research Article
  • Published:
Virologica Sinica

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) shows characteristic antibody-dependent enhancement (ADE) of infection and causes porcine systemic inflammation, which is similar to a type I allergic reaction; however, the role of porcine FcεRI in ADE is still unclear. In this study, the expression of different Fc receptors (FcRs) on macrophages was investigated in a PRRSV 3D4/21 cell infection model in the presence or absence of PRRSV antibody. The transcription level of FcγII and FcεRI was significantly up-regulated under PRRSV-antibody complex infection. Internalization and proliferation of PRRSV were promoted by the ADE mechanism when FcεRI was expressed in permissive 3D4/21 cells and the non-permissive cell line HEK 293T. Transcriptome sequencing data showed that the expression levels of AKT, ERK and other signal molecules in the anti-inflammatory pathway were significantly increased, especially in the cells infected with the PRRSV-antibody immune complex. Inflammatory regulatory molecules such as PLA2G6, LOX, TRPM8 and TRPM4 were significantly up-regulated following PRRSV infection but significantly down-regulated in the cells infected with the PRRSV-antibody immune complex. Our results demonstrated that FcεRI could be involved in PRRSV ADE, the antigen presenting process and regulation of the inflammatory response during PRRSV infection, which provides new insights into PRRSV infection mediated by FcεRI and the PRRSV-antibody immune complex.

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

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

References

  • Allende R, Lewis TL, Lu Z, Rock DL, Kutish GF, Ali A, Doster AR, Osorio FA (1999) North American and European porcine reproductive and respiratory syndrome viruses differ in non-structural protein coding regions. J Gen Virol 80:307–315

    Article  PubMed  CAS  Google Scholar 

  • Arce C, Ramirez-Boo M, Lucena C, Garrido JJ (2010) Innate immune activation of swine intestinal epithelial cell lines (IPEC-J2 and IPI-2I) in response to LPS from Salmonella typhimurium. Comp Immunol Microbiol Infect Dis 33:161–174

    Article  PubMed  CAS  Google Scholar 

  • Auray G, Lachance C, Wang Y, Gagnon CA, Segura M, Gottschalk M (2016) Transcriptional analysis of PRRSV-infected porcine dendritic cell response to streptococcus suis infection reveals up-regulation of inflammatory-related genes expression. PLoS ONE 11:e0156019

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bao D, Wang R, Qiao S, Wan B, Wang Y, Liu M, Shi X, Guo J, Zhang G (2013) Antibody-dependent enhancement of PRRSV infection down-modulates TNF-α and IFN-β transcription in macrophages. Vet Immunol Immunopathol 156:128–134

    Article  PubMed  CAS  Google Scholar 

  • Bournazos S, Ravetch JV (2017) Fcγ receptor function and the design of vaccination strategies. Immunity 47:224–233

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Chen SS, Bohn JW, Liu FT, Katz DH (1981) Murine lymphocytes expressing Fc receptors for IgE (FcRε). I. Conditions for inducing FcRε + lymphocytes and inhibition of the inductive events by suppressive factor of allergy (SFA). J Immunol 127:166–173

    PubMed  CAS  Google Scholar 

  • Chew WS, Ong WY (2016) Regulation of calcium-independent phospholipase A2 expression by Adrenoceptors and Sterol regulatory element binding protein-potential crosstalk between sterol and Glycerophospholipid mediators. Mol Neurobiol 53: 500-517

    Article  PubMed  CAS  Google Scholar 

  • Christianson WT, Choi CS, Collins JE, Molitor TW, Morrison RB, Joo HS (1993) Pathogenesis of porcine reproductive and respiratory syndrome virus infection in mid-gestation sows and fetuses. Can J Vet Res 57:262–268

    PubMed  PubMed Central  CAS  Google Scholar 

  • Daëron M, Néauport-Sautès C, Yodoi J, Moncuit J, Fridman WH (1985) Receptors for immunoglobulin isotypes (FcR) on murine T cells. II. Multiple FcR induction on hybridoma T cell clones. Eur J Immunol 15:668–674

    Article  PubMed  Google Scholar 

  • de Witte SFH, Merino AM, Franquesa M, Strini T, van Zoggel JAA, Korevaar SS, Luk F, Gargesha M, O’Flynn L, Roy D, Elliman SJ, Newsome PN, Baan CC, Hoogduijn MJ (2017) Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease. Stem Cell Res Ther 8:140

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dhaliwal B, Pang MO, Keeble AH, James LK, Gould HJ, McDonnell JM, Sutton BJ, Beavil AJ (2017) IgE binds asymmetrically to its B cell receptor CD23. Sci Rep 7:45533

    Article  PubMed  PubMed Central  Google Scholar 

  • Dong J, Xu S, Wang J, Luo R, Wang D, **ao S, Fang L, Chen H, Jiang Y (2015) Porcine reproductive and respiratory syndrome virus 3C protease cleaves the mitochondrial antiviral signalling complex to antagonize IFN-β expression. J Gen Virol 96:3049–3058

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Du Y, Du T, Shi Y, Zhang A, Zhang C, Diao Y, ** G, Zhou EM (2016) Synthetic Toll-like receptor 7 ligand inhibits porcine reproductive and respiratory syndrome virus infection in primary porcine alveolar macrophages. Antivir Res 131:9–18

    Article  PubMed  CAS  Google Scholar 

  • Duan X, Nauwynck HJ, Pensaert MB (1997) Virus quantification and identification of cellular targets in the lungs and lymphoid tissues of pigs at different time intervals after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV). Vet Microbiol 56:9–19

    Article  PubMed  CAS  Google Scholar 

  • Gao F, Qu Z, Li L, Yu L, Jiang Y, Zhou Y, Yang S, Zheng H, Huang Q, Tong W, Tong G (2016) Recombinant porcine reproductive and respiratory syndrome virus expressing luciferase genes provide a new indication of viral propagation in both permissive and target cells. Res Vet Sci 107:132–140

    Article  PubMed  Google Scholar 

  • Gu W, Guo L, Yu H, Niu J, Huang M, Luo X, Li R, Tian Z, Feng L, Wang Y (2015) Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection. J Gen Virol 96:1712–1722

    Article  PubMed  CAS  Google Scholar 

  • Guo J, Chang G, Zhang K, Xu L, ** D, Bilal MS, Shen X (2017) Rumen-derived lipopolysaccharide provoked inflammatory injury in the liver of dairy cows fed a high-concentrate diet. Oncotarget 8:46769–46780

    PubMed  PubMed Central  Google Scholar 

  • Halstead SB, O’Rourke EJ (1977) Antibody-enhanced dengue virus infection in primate leukocytes. Nature 265:739–741

    Article  PubMed  CAS  Google Scholar 

  • Huang YW, Fang Y, Meng XJ (2009) Identification and characterization of a porcine monocytic cell line supporting porcine reproductive and respiratory syndrome virus (PRRSV) replication and progeny virion production by using an improved DNA-launched PRRSV reverse genetics system. Virus Res 145:1–8

    Article  PubMed  CAS  Google Scholar 

  • Khan HA, Ahmad MZ, Khan JA, Arshad MI (2017) Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance. Hepatobiliary Pancreat Dis Int 16:245–256

    Article  PubMed  Google Scholar 

  • Kimberly RP, Wu J, Gibson AW, Su K, Qin H, Li X, Edberg JC (2002) Diversity and duplicity: human FCγ receptors in host defense and autoimmunity. Immunol Res 26:177–189

    Article  PubMed  CAS  Google Scholar 

  • Kozyreva TV, Khramova GM, Voronova IP, Evtushenko AA (2016) The influence of cooling and TRPM8 ion channel activation on the level of pro-inflammatory cytokines in normotensive and hypertensive rats. J Therm Biol 61:119–124

    Article  PubMed  CAS  Google Scholar 

  • Lee YJ, Park CK, Nam E, Kim SH, Lee OS, du Lee S, Lee C (2010) Generation of a porcine alveolar macrophage cell line for the growth of porcine reproductive and respiratory syndrome virus. J Virol Methods 163:410–415

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Wang A, Qiao S, Zhang G, ** J, You L, Tian X, Li Q, Zhang L, Guo J (2010) Cloning and characterization of ovine immunoglobulin G Fc receptor II (FcγRII). Vet Immunol Immunopathol 133:243–249

    Article  PubMed  CAS  Google Scholar 

  • Lunney JK, Fang Y, Ladinig A, Chen N, Li Y, Rowland B, Renukaradhya GJ (2016) Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): pathogenesis and interaction with the immune system. Annu Rev Anim Biosci 4:129–154

    Article  PubMed  CAS  Google Scholar 

  • McCann PA, Amirfeyz R, Wakeley C, Bhatia R (2010) The volar anatomy of the distal radius—an MRI study of the FCR approach. Injury 41:1012–1014

    Article  PubMed  CAS  Google Scholar 

  • Nagai H, Yakuo I, Yamada H, Inagaki N, Goto S, Koda A (1986) Effect of cinnarizine on IgE antibody mediated allergic reaction in mice and rats. J Pharmacobiodyn 9:923–927

    Article  PubMed  CAS  Google Scholar 

  • Neau DB, Bender G, Boeglin WE, Bartlett SG, Brash AR, Newcomer ME (2014) Crystal structure of a lipoxygenase in complex with substrate: the arachidonic acid-binding site of 8R-lipoxygenase. J Biol Chem 289: 31905–31913

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nedumpun T, Wongyanin P, Sirisereewan C, Ritprajak P, Palaga T, Thanawongnuwech R, Suradhat S (2017) Interleukin-1 receptor antagonist: an early immunomodulatory cytokine induced by porcine reproductive and respiratory syndrome virus. J Gen Virol 98:77–88

    Article  PubMed  CAS  Google Scholar 

  • Novakovic P, Harding JC, Ladinig A, Al-Dissi AN, MacPhee DJ, Detmer SE (2016) Relationships of CD163 and CD169 positive cell numbers in the endometrium and fetal placenta with type 2 PRRSV RNA concentration in fetal thymus. Vet Res 47:76

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park YH, Miyama-Inaba M, Suzuki T, Masuda T, Yoshida Y, Uchino H (1984) Immunological characterization of FcRγ bearing and nonbearing B cells: functional modulation of immune complexes. Cell Immunol 83:340–350

    Article  PubMed  CAS  Google Scholar 

  • Peterfy H, Toth G, Pecht I, Erdei A (2008) C3a-derived peptide binds to the type I FcεR and inhibits proximal-coupling signal processes and cytokine secretion by mast cells. Int Immunol 20:1239–1245

    Article  PubMed  CAS  Google Scholar 

  • Platzer B, Ruiter F, van der Mee J, Fiebiger E (2011) Soluble IgE receptors–elements of the IgE network. Immunol Lett 141:36–44

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Prather RS, Whitworth KM, Schommer SK, Wells KD (2017) Genetic engineering alveolar macrophages for host resistance to PRRSV. Vet Microbiol. https://doi.org/10.1016/j.vetmic.2017.01.036

    Article  PubMed  Google Scholar 

  • Qiao C, Guo L, Sun J, Li Y, Lin Z, Lv M, Feng J, Shen B (2009) Suitable transmembrane domain significantly increase the surface-expression level of Fc(ε)RIα in 293T cells. J Biotechnol 139:195–202

    Article  PubMed  CAS  Google Scholar 

  • Qiao S, Liu Y, Zhang J, Yang S, Wan B, Shi P, Zhang H, Guo J, Zhang G (2010) Genetic characterization and ligand specificity of the ovine Fc gamma receptor I (ovFcγRI). Vet Immunol Immunopathol 137:317–321

    Article  PubMed  CAS  Google Scholar 

  • Qiao S, Jiang Z, Tian X, Wang R, **ng G, Wan B, Bao D, Liu Y, Hao H, Guo J, Zhang G (2011) Porcine FcγRIIb mediates enhancement of porcine reproductive and respiratory syndrome virus (PRRSV) infection. PLoS ONE 6:e28721

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rascon-Castelo E, Burgara-Estrella A, Resendiz-Sandoval M, Hernandez-Lugo A, Hernandez J (2015) immune response of multiparous hyper-immunized sows against peptides from non-structural and structural proteins of PRRSV. Vaccines (Basel) 3:973–987

    Article  CAS  Google Scholar 

  • Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Epidemiol 27:493–497

    Article  Google Scholar 

  • Sinha A, Lin K, Hemann M, Shen H, Beach NM, Ledesma C, Meng XJ, Wang C, Halbur PG, Opriessnig T (2012) ORF1 but not ORF2 dependent differences are important for in vitro replication of PCV2 in porcine alveolar macrophages singularly or coinfected with PRRSV. Vet Microbiol 158:95–103

    Article  PubMed  CAS  Google Scholar 

  • Snijder EJ, Meulenberg JJ (1998) The molecular biology of arteriviruses. J Gen Virol 79(Pt 5):961–979

    Article  PubMed  CAS  Google Scholar 

  • Suzuki K, Hirose T, Matsuda H, Hasegawa S, Okumura K, Ra C (1998) The Fc receptor (FcR)γ subunit is essential for IgE-binding activity of cell-surface expressed chimeric receptor molecules constructed from human high-affinity IgE receptor (FcεRI) α and FcRγ subunits. Mol Immunol 35:259–270

    Article  PubMed  CAS  Google Scholar 

  • Takayama G, Ohtani M, Minowa A, Matsuda S, Koyasu S (2013) Class I PI3 K-mediated Akt and ERK signals play a critical role in FcεRI-induced degranulation in mast cells. Int Immunol 25:215–220

    Article  PubMed  CAS  Google Scholar 

  • Terada T, Takahashi T, Arikawa H, Era S (2016) Analysis of the conformation and thermal stability of the high-affinity IgE Fc receptor β chain polymorphic proteins. Biosci Biotechnol Biochem 80:1356–1361

    Article  PubMed  CAS  Google Scholar 

  • Tian X, Feng Y, Zhao T, Peng H, Yan J, Qi J, Jiang F, Tian K, Gao F (2007) Molecular cloning, expression, purification and crystallographic analysis of PRRSV 3CL protease. Acta Crystallogr, Sect F: Struct Biol Cryst Commun 63:720–722

    Article  CAS  Google Scholar 

  • Tirado SM, Yoon KJ (2003) Antibody-dependent enhancement of virus infection and disease. Viral Immunol 16:69–86

    Article  PubMed  CAS  Google Scholar 

  • Uddin MJ, Nuro-Gyina PK, Islam MA, Tesfaye D, Tholen E, Looft C, Schellander K, Cinar MU (2012) Expression dynamics of Toll-like receptors mRNA and cytokines in porcine peripheral blood mononuclear cells stimulated by bacterial lipopolysaccharide. Vet Immunol Immunopathol 147:211–222

    Article  PubMed  CAS  Google Scholar 

  • Wang YQ, Liu Y, Wang YX, Wu YJ, Jia PY, Shan JJ, Wu J, Ma GH, Su ZG (2016) The potential adjuvanticity of quaternized chitosan hydrogel based microparticles for porcine reproductive and respiratory syndrome virus inactivated vaccine. Int Immunopharmacol 39:84–91

    Article  PubMed  CAS  Google Scholar 

  • Wensvoort G, de Kluyver EP, Pol JM, Wagenaar F, Moormann RJ, Hulst MM, Bloemraad R, den Besten A, Zetstra T, Terpstra C (1992) Lelystad virus, the cause of porcine epidemic abortion and respiratory syndrome: a review of mystery swine disease research at Lelystad. Vet Microbiol 33:185–193

    Article  PubMed  CAS  Google Scholar 

  • Wilson BS, Pfeiffer JR, Oliver JM (2002) FcεRI signaling observed from the inside of the mast cell membrane. Mol Immunol 38:1259–1268

    Article  PubMed  CAS  Google Scholar 

  • Yao Y, Wang L, ** P, Li N, Meng Y, Wang C, Xu M, Zhang Y, Bian J, Deng X (2017) Methane alleviates carbon tetrachloride induced liver injury in mice: anti-inflammatory action demonstrated by increased PI3 K/Akt/GSK-3β-mediated IL-10 expression. J Mol Histol 48:301–310

    Article  PubMed  CAS  Google Scholar 

  • Yoon KJ, Wu LL, Zimmerman JJ, Hill HT, Platt KB (1996) Antibody-dependent enhancement (ADE) of porcine reproductive and respiratory syndrome virus (PRRSV) infection in pigs. Viral Immunol 9:51–63

    Article  PubMed  CAS  Google Scholar 

  • Yoon KJ, Wu LL, Zimmerman JJ, Platt KB (1997) Field isolates of porcine reproductive and respiratory syndrome virus (PRRSV) vary in their susceptibility to antibody dependent enhancement (ADE) of infection. Vet Microbiol 55:277–287

    Article  PubMed  CAS  Google Scholar 

  • Yuan S, Murtaugh MP, Schumann FA, Mickelson D, Faaberg KS (2004) Characterization of heteroclite subgenomic RNAs associated with PRRSV infection. Virus Res 105:75–87

    Article  PubMed  CAS  Google Scholar 

  • Yuste M, Fernandez-Caballero T, Prieto C, Alvarez B, Martinez-Lobo J, Simarro I, Castro JM, Alonso F, Ezquerra A, Dominguez J, Revilla C (2017) Splenic CD163 + macrophages as targets of porcine reproductive and respiratory virus: role of Siglecs. Vet Microbiol 198:72–80

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Chen J, Wang D, Li N, Qin Y, Du D, Yang M, **a P (2016) Ligation of porcine Fc gamma receptor III inhibits levels of antiviral cytokine in response to PRRSV infection in vitro. Res Vet Sci 105:47–52

    Article  PubMed  CAS  Google Scholar 

  • Zhao J, Feng N, Li Z, Wang P, Qi Z, Liang W, Zhou X, Xu X, Liu B (2016) 2′,5′-Oligoadenylate synthetase 1(OAS1) inhibits PRRSV replication in Marc-145 cells. Antiviral Res 132:268–273

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (31272540) and the underprop project of Tian** Science and Technology Committee in China (16YFZCNC00640).

Author information

Author notes

  1. Peidian Shi, Lilin Zhang, Jiashun Wang have contributed equally to this work.

Authors and Affiliations

  1. School of Life Sciences, Tian** University, 300072, Tian**, China

    Peidian Shi, Lilin Zhang, Jiashun Wang, Dong Lu, Yi Li, Jie Ren, Menglu Shen, Lei Zhang & **hai Huang

Authors
  1. Peidian Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lilin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiashun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jie Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Menglu Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. **hai Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JH conceived and designed the experiments. PS, JW, DL, MS, Lilin Zhang, YL, Lei Zhang performed the experiments. JW and JR analyzed the data. JW and JH wrote the paper. JH, Lei Zhang checked and finalized the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lei Zhang or **hai Huang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

Animal experiments were performed in compliance with the regulations set by Tian** University Institutional Animal Care and Use Committee and were approved by the veterinarian authorities of Tian** Animal Inspection Institute. This study was carried out in strict accordance with the guidelines in the Guide for the Care and Use of Laboratory Animals in China.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 448 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, P., Zhang, L., Wang, J. et al. Porcine FcεRI Mediates Porcine Reproductive and Respiratory Syndrome Virus Multiplication and Regulates the Inflammatory Reaction. Virol. Sin. 33, 249–260 (2018). https://doi.org/10.1007/s12250-018-0032-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12250-018-0032-3

Keywords

Search

Navigation