Skip to main content

Advertisement

SpringerLink
Log in

The glycosyltransferase ST3GAL2 modulates virus proliferation and the inflammation response in porcine reproductive and respiratory syndrome virus infection

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

Abstract

β-galactoside α-2,3-sialyltransferase 2 (ST3GAL2) is a member of the sialyltransferase family that mediates terminal modification of glycoproteins and glycolipids. ST3GAL2 has been found to play a role in obesity, aging, and malignant diseases. In this study, we cloned porcine ST3GAL2 (pST3GAL2) from porcine alveolar macrophages (PAMs), and its role in porcine reproductive and respiratory syndrome virus (PRRSV) infection was investigated by transcriptome analysis. pST3GAL2 was found to be located in the Golgi apparatus, and it was expressed at high levels in PRRSV-infected PAMs. Overexpression of pST3GAL2 resulted in a slight increase in PRRSV proliferation, and the interaction between pST3GAL2 and GP2a of PRRSV was detected by coimmunoprecipitation and confocal microscopy. The expression of pro-inflammatory cytokines (IFN-β, IL-2, IL-6, IL-18, IL-1β and TNF-α) was significantly inhibited in pST3GAL2-overexpressing, PRRSV-infected cells and upregulated in PRRSV-infected pST3GAL2-knockout cells, while the pattern of expression of anti-inflammatory cytokines (IL-4 and IL-10) was diametrically opposite. Our results demonstrate that the regulation of pST3GAL2 plays an important role in PRRSV proliferation and functional alterations in virus-infected cells. These results contribute to our understanding of the role of β-galactoside α-2,3-sialyltransferase 2 in antiviral immunity.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Lopez PH, Aja S, Aoki K, Seldin MM, Lei X, Ronnett GV, Wong GW, Schnaar RL (2017) Mice lacking sialyltransferase ST3Gal-II develop late-onset obesity and insulin resistance. Glycobiology 27:129–139

    Article  CAS  Google Scholar 

  2. Takashima S, Tachida Y, Nakagawa T, Hamamoto T, Tsuji S (1999) Quantitative analysis of expression of mouse sialyltransferase genes by competitive PCR. Biochem Biophys Res Commun 260:23–27

    Article  CAS  Google Scholar 

  3. Suzuki O, Kanai T, Nishikawa T, Yamamoto Y, Noguchi A, Takimoto K, Koura M, Noguchi Y, Uchio-Yamada K, Tsuji S, Matsuda J (2011) Adult onset cardiac dilatation in a transgenic mouse line with Galbeta 1,3GalNAc alpha2,3-sialyltransferase II (ST3Gal-II) transgenes: a new model for dilated cardiomyopathy. Proc Jpn Acad Ser B Phys Biol Sci 87:550–562

  4. Schjoldager KT, Narimatsu Y, Joshi HJ, Clausen H (2020) Global view of human protein glycosylation pathways and functions. Nat Rev Mol Cell Biol 21:729–749

    Article  CAS  Google Scholar 

  5. Zhang J, Ten Dijke P, Wuhrer M, Zhang T (2021) Role of glycosylation in TGF-beta signaling and epithelial-to-mesenchymal transition in cancer. Protein Cell 12:89–106

    Article  CAS  Google Scholar 

  6. Alisson-Silva F, de Carvalho RD, Vairo L, Asensi KD, Vasconcelos-dos-Santos A, Mantuano NR, Dias WB, Rondinelli E, Goldenberg RC, Urmenyi TP, Todeschini AR (2014) Evidences for the involvement of cell surface glycans in stem cell pluripotency and differentiation. Glycobiology 24:458–468

    Article  CAS  Google Scholar 

  7. Ruggiero FM, Vilcaes AA, Iglesias-Bartolome R, Daniotti JL (2015) Critical role of evolutionarily conserved glycosylation at Asn211 in the intracellular trafficking and activity of sialyltransferase ST3Gal-II. Biochem J 469:83–95

    Article  CAS  Google Scholar 

  8. York IA, Stevens J, Alymova IV (2019) Influenza virus N-linked glycosylation and innate immunity. Biosci Rep 2019:39

  9. Bagdonaite I, Norden R, Joshi HJ, King SL, Vakhrushev SY, Olofsson S, Wandall HH (2016) Global mapping of O-glycosylation of varicella zoster virus, human cytomegalovirus, and Epstein-barr virus. J Biol Chem 291:12014–12028

    Article  CAS  Google Scholar 

  10. Wasik BR, Barnard KN, Parrish CR (2016) Effects of sialic acid modifications on virus binding and infection. Trends Microbiol 24:991–1001

    Article  CAS  Google Scholar 

  11. Khan AA, Bose C, Yam LS, Soloski MJ, Rupp F (2001) Physiological regulation of the immunological synapse by agrin. Science 292:1681–1686

    Article  CAS  Google Scholar 

  12. Zimmerman JJ, Yoon KJ, Wills RW, Swenson SLJVM (1997) General overview of PRRSV: a perspective from the United States. Vet Microbiol 55:187–196

    Article  CAS  Google Scholar 

  13. Yoon KJ, Wu L-L, Zimmerman JJ, Hill HT, Platt KBJVI (2019) Antibody-dependent enhancement (ADE) of porcine reproductive and respiratory syndrome virus (PRRSV) infection in pigs. Viral Immunol 9:51–63

  14. Guo Z, Chen XX, Li R, Qiao S, Zhang G (2018) The prevalent status and genetic diversity of porcine reproductive and respiratory syndrome virus in China: a molecular epidemiological perspective. Virol J 15:2

    Article  Google Scholar 

  15. Conzelmann KK, Visser N, Van Woensel P, Thiel HJ (1993) Molecular characterization of porcine reproductive and respiratory syndrome virus, a member of the arterivirus group. Virology 193:329–339

    Article  CAS  Google Scholar 

  16. Wang F, Qiu H, Zhang Q, Peng Z, Liu B (2012) Association of two porcine reproductive and respiratory syndrome virus (PRRSV) receptor genes, CD163 and SN with immune traits. Mol Biol Rep 39:3971–3976

    Article  CAS  Google Scholar 

  17. Yoo D, Wootton S (2001) Homotypic interactions of the nucleocapsid protein of porcine reproductive and respiratory syndrome virus (PRRSV). Adv Exp Med Biol 494:627–632

    Article  CAS  Google Scholar 

  18. Royaee AR, Husmann RJ, Dawson HD, Calzada-Nova G, Schnitzlein WM, Zuckermann FA, Lunney JK (2004) Deciphering the involvement of innate immune factors in the development of the host response to PRRSV vaccination. Vet Immunol Immunopathol 102:199–216

    Article  CAS  Google Scholar 

  19. Tu L, Banfield DK (2010) Localization of Golgi-resident glycosyltransferases. Cell Mol Life Sci 67:29–41

    Article  CAS  Google Scholar 

  20. Maginnis MS (2018) Virus-receptor interactions: the key to cellular invasion. J Mol Biol 430:2590–2611

    Article  CAS  Google Scholar 

  21. de Graaf M, Fouchier RA (2014) Role of receptor binding specificity in influenza A virus transmission and pathogenesis. EMBO J 33:823–841

    Article  Google Scholar 

  22. Chen XX, Quan R, Guo XK, Gao L, Shi J, Feng WH (2014) Up-regulation of pro-inflammatory factors by HP-PRRSV infection in microglia: implications for HP-PRRSV neuropathogenesis. Vet Microbiol 170:48–57

    Article  CAS  Google Scholar 

  23. Charerntantanakul W, Pongjaroenkit S (2018) Co-administration of saponin quil A and PRRSV-1 modified-live virus vaccine up-regulates gene expression of type I interferon-regulated gene, type I and II interferon, and inflammatory cytokines and reduces viremia in response to PRRSV-2 challenge. Vet Immunol Immunopathol 205:24–34

    Article  CAS  Google Scholar 

  24. Watanabe Y, Bowden TA, Wilson IA, Crispin M (2019) Exploitation of glycosylation in enveloped virus pathobiology. Biochim Biophys Acta Gen Subj 1863:1480–1497

    Article  CAS  Google Scholar 

  25. Oinam L, Changarathil G, Raja E, Ngo YX, Tateno H, Sada A, Yanagisawa H (2020) Glycome profiling by lectin microarray reveals dynamic glycan alterations during epidermal stem cell aging. Aging Cell 19:e13190

  26. Shi X, Fan X, Nie S, Kou L, Zhang X, Liu H, Ji S, Deng R, Wang A, Zhang G (2019) Identification of a linear B-cell epitope on glycoprotein (GP) 2a of porcine reproductive and respiratory syndrome virus (PRRSV). Int J Biol Macromol 139:1288–1294

    Article  CAS  Google Scholar 

  27. Das PB, Dinh PX, Ansari IH, de Lima M, Osorio FA, Pattnaik AK (2010) The minor envelope glycoproteins GP2a and GP4 of porcine reproductive and respiratory syndrome virus interact with the receptor CD163. J Virol 84:1731–1740

    Article  CAS  Google Scholar 

  28. Calvert JG, Slade DE, Shields SL, Jolie R, Mannan RM, Ankenbauer RG, Welch SK (2007) CD163 expression confers susceptibility to porcine reproductive and respiratory syndrome viruses. J Virol 81:7371–7379

    Article  CAS  Google Scholar 

  29. Wissink EHJ, Kroese MV, Maneschijn-Bonsing JG, Meulenberg JJM, van Rijn PA, Rijsewijk FAM, Rottier PJM (2004) Significance of the oligosaccharides of the porcine reproductive and respiratory syndrome virus glycoproteins GP2a and GP5 for infectious virus production. J Gen Virol 85:3715–3723

    Article  CAS  Google Scholar 

  30. 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  CAS  Google Scholar 

  31. Huso DL, Narayan O, Hart GW (1988) Sialic acids on the surface of caprine arthritis-encephalitis virus define the biological properties of the virus. J Virol 62:1974–1980

    Article  CAS  Google Scholar 

  32. Johnson WE, Sanford H, Schwall L, Burton DR, Parren PW, Robinson JE, Desrosiers RC (2003) Assorted mutations in the envelope gene of simian immunodeficiency virus lead to loss of neutralization resistance against antibodies representing a broad spectrum of specificities. J Virol 77:9993–10003

    Article  CAS  Google Scholar 

  33. Zhang L, Wang CC (2014) Inflammatory response of macrophages in infection. Hepatobiliary Pancreat Dis Int 13:138–152

    Article  CAS  Google Scholar 

  34. Porcheray F, Viaud S, Rimaniol AC, Leone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G (2005) Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 142:481–489

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P (2003) Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol 325:979–989

    Article  CAS  Google Scholar 

  36. Wachholz PA, Soni NK, Till SJ, Durham SR (2003) Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol 112:915–922

    Article  CAS  Google Scholar 

  37. Ravetch JV, Bolland S (2001) IgG Fc receptors. Annu Rev Immunol 19:275–290

    Article  CAS  Google Scholar 

  38. Pagan JD, Kitaoka M, Anthony RM (2018) Engineered sialylation of pathogenic antibodies in vivo attenuates autoimmune disease. Cell 172:564–577 e13.

  39. Moratz J, Klepel F, Ravoo BJ (2017) Dynamic glycosylation of liposomes by thioester exchange. Org Biomol Chem 15:5089–5094

    Article  CAS  Google Scholar 

  40. Russell A, Adua E, Ugrina I, Laws S, Wang W (2018) Unravelling Immunoglobulin G Fc N-glycosylation: a dynamic marker potentiating predictive, preventive and personalised medicine. Int J Mol Sci 2018:19

  41. Nishikaze T (2019) Sialic acid derivatization for glycan analysis by mass spectrometry. Proc Jpn Acad Ser B Phys Biol Sci 95:523–537

    Article  Google Scholar 

  42. Huang S, Day TW, Choi MR, Safa AR (2009) Human beta-galactoside alpha-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity. Mol Cell Biochem 331:81–88

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Key Projects of Science and Technology Support Grant of Tianjin in China (20YFZCSN00340) and the National Innovation Center for Synthetic Biotechnology (TSBICIP-KJGG-014).

Author information

Author notes

  1. Xiaoyang Li, Yanyu Guo and Yinna Song contributed equally to this work.

Authors and Affiliations

  1. School of Life Sciences, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, China

    Xiaoyang Li, Yanyu Guo, Yinna Song, Ruiqi Sun, Min Zhu, Zheng Tan, Umm E Swaiba, Lilin Zhang & Jinhai Huang

Authors
  1. Xiaoyang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanyu Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yinna Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ruiqi Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Min Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zheng Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Umm E Swaiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lilin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jinhai Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the experiments: JH H. Performed the experiments: XY L, YY G, YN S, XY L, RQ S, M Z, Z T, UE S, LL Z and JH H. Analyzed the data: JQ W, JH H. Contributed reagents/materials /analysis tools: JH H. Wrote the paper: JQ W, and JH H.

Corresponding author

Correspondence to Jinhai Huang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Handling Editor: Diego G. Diel.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Guo, Y., Song, Y. et al. The glycosyltransferase ST3GAL2 modulates virus proliferation and the inflammation response in porcine reproductive and respiratory syndrome virus infection. Arch Virol 166, 2723–2732 (2021). https://doi.org/10.1007/s00705-021-05180-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-021-05180-1

Search

Navigation