Skip to main content

Advertisement

Log in

Transcriptome sequencing analysis of porcine alveolar macrophages infected with PRRSV strains to elucidate virus pathogenicity and immune evasion strategies

  • Original Article
  • Published:
VirusDisease Aims and scope Submit manuscript

Abstract

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) causes a serious disease to the swine industry worldwide. To understand the mechanisms of HP-PRRSV infection, RNA-seq-based transcriptome analyses were performed on porcine alveolar macrophages (PAMs) infected with a HP-PRRSV strain (TJ), a less virulent strain of a classical lineage (CH-1a), and a vaccine strain TJM-F92. Gene ontology, Kyoto Encyclopedia of Genes and Genomes analyses indicate that TJM-F92 led to significant up-regulation of gene expression for proteins associated with membrane-bound organelles. The differentially expressed genes of HP-PRRSV TJ-infected PAM cells were up-regulated in the special G-protein coupled receptor. The six cytokines were tested by real time Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The relative expression levels showed the same trend of expression difference. Significant up-regulation of TMEM173 plays an important role in the cytosolic DNA-sensing pathway and the RIG-I-like receptor signaling pathway in TJM-F92 infected PAM cells. These data provide new insight into PRRSV pathogenicity and immune evasion strategies.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. An TQ, Zhou YJ, Liu GQ, Tian ZJ, Li J, Qiu HJ, Tong GZ. Genetic diversity and phylogenetic analysis of glycoprotein 5 of PRRSV isolates in mainland China from 1996 to 2006: coexistence of two NA-subgenotypes with great diversity. Vet Microbiol. 2007;123(1–3):43–52.

    Article  CAS  Google Scholar 

  2. Badaoui B, Rutigliano T, Anselmo A, Vanhee M, Nauwynck H, Giuffra E, Botti S. RNA-sequence analysis of primary alveolar macrophages after in vitro infection with porcine reproductive and respiratory syndrome virus strains of differing virulence. PLoS ONE. 2014;9(3):e91918.

    Article  Google Scholar 

  3. Barber GN. STING-dependent cytosolic DNA sensing pathways. Trends Immunol. 2014;35(2):88–93.

    Article  CAS  Google Scholar 

  4. Benfield DA, Nelson E, Collins JE, Harris L, Goyal SM, Robison D, Christianson WT, Morrison RB, Gorcyca D, Chladek D. Characterization of swine infertility and respiratory syndrome (SIRS) virus (isolate ATCC VR-2332). J Vet Diagn Invest. 1992;4(2):127–33.

    Article  CAS  Google Scholar 

  5. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodol). 1995;57(1):289–300.

    Google Scholar 

  6. Cong P, Xiao S, Chen Y, Wang L, Gao J, Li M, He Z, Guo Y, Zhao G, Zhang X, et al. Integrated miRNA and mRNA transcriptomes of porcine alveolar macrophages (PAM cells) identifies strain-specific miRNA molecular signatures associated with H-PRRSV and N-PRRSV infection. Mol Biol Rep. 2014;41(9):5863–75.

    Article  CAS  Google Scholar 

  7. Fang Y, Fang L, Wang Y, Lei Y, Luo R, Wang D, Chen H, Xiao S. Porcine reproductive and respiratory syndrome virus nonstructural protein 2 contributes to NF-kappaB activation. Virol J. 2012;9(1):83.

    Article  CAS  Google Scholar 

  8. Firth AE, Zevenhoven-Dobbe JC, Wills NM, Go YY, Balasuriya UB, Atkins JF, Snijder EJ, Posthuma CC. Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production. J Gen Virol. 2011;92(Pt 5):1097–106.

    Article  CAS  Google Scholar 

  9. Forsberg R, Storgaard T, Nielsen HS, Oleksiewicz MB, Cordioli P, Sala G, Hein J, Botner A. The genetic diversity of European type PRRSV is similar to that of the North American type but is geographically skewed within Europe. Virology. 2002;299(1):38–47.

    Article  CAS  Google Scholar 

  10. Guo BQ, Chen ZS, Liu WX, Cui YZ, Kong LD. Isolation and identification of porcine reproductory and respiratory syndrome (PRRS) virus from aborted fetuses suspected of PRRS. Chin J Infect Diseases Anim Poult. 1996;2:1–5.

    Google Scholar 

  11. Heald R, Cohen-Fix O. Morphology and function of membrane-bound organelles. Curr Opin Cell Biol. 2014;26:79–86.

    Article  CAS  Google Scholar 

  12. Holm CK, Jensen SB, Jakobsen MR, Cheshenko N, Horan KA, Moeller HB, Gonzalez-Dosal R, Rasmussen SB, Christensen MH, Yarovinsky TO, et al. Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nat Immunol. 2012;13(8):737–43.

    Article  CAS  Google Scholar 

  13. Islam MA, Grosse-Brinkhaus C, Proll MJ, Uddin MJ, Aqter Rony S, Tesfaye D, Tholen E, Hoelker M, Schellander K, Neuhoff C. PBMC transcriptome profiles identifies potential candidate genes and functional networks controlling the innate and the adaptive immune response to PRRSV vaccine in Pietrain pig. PLoS ONE. 2017;12(3):e0171828.

    Article  Google Scholar 

  14. Islam MA, Grosse-Brinkhaus C, Proll MJ, Uddin MJ, Rony SA, Tesfaye D, Tholen E, Holker M, Schellander K, Neuhoff C. Deciphering transcriptome profiles of peripheral blood mononuclear cells in response to PRRSV vaccination in pigs. BMC Genomics. 2016;17(1):641.

    Article  Google Scholar 

  15. Islam MA, Neuhoff C, Aqter Rony S, Grosse-Brinkhaus C, Uddin MJ, Holker M, Tesfaye D, Tholen E, Schellander K, Proll-Cornelissen MJ. PBMCs transcriptome profiles identified breed-specific transcriptome signatures for PRRSV vaccination in German Landrace and Pietrain pigs. PLoS ONE. 2019;14(9):e0222513.

    Article  CAS  Google Scholar 

  16. Jing H, Fang L, Wang D, Ding Z, Luo R, Chen H, Xiao S. Porcine reproductive and respiratory syndrome virus infection activates NOD2-RIP2 signal pathway in MARC-145 cells. Virology. 2014;458–459:162–71.

    Article  Google Scholar 

  17. Johnson CR, Griggs TF, Gnanandarajah J, Murtaugh MP. Novel structural protein in porcine reproductive and respiratory syndrome virus encoded by an alternative ORF5 present in all arteriviruses. J Gen Virol. 2011;92(Pt 5):1107–16.

    Article  CAS  Google Scholar 

  18. Kristiansen K. Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis approaches to receptor structure and function. Pharmacol Ther. 2004;103(1):21–80.

    Article  CAS  Google Scholar 

  19. Leng X, Li Z, Xia M, He Y, Wu H. Evaluation of the efficacy of an attenuated live vaccine against highly pathogenic porcine reproductive and respiratory syndrome virus in young pigs. Clin Vaccine Immunol CVI. 2012;19(8):1199–206.

    Article  CAS  Google Scholar 

  20. Liang W, Ji L, Zhang Y, Zhen Y, Zhang Q, Xu X, Liu B. Transcriptome differences in porcine alveolar macrophages from tongcheng and large white pigs in response to highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) infection. Int J Mol Sci. 2017;18(7):1475.

    Article  Google Scholar 

  21. Loo YM, Gale M Jr. Immune signaling by RIG-I-like receptors. Immunity. 2011;34(5):680–92.

    Article  CAS  Google Scholar 

  22. Meulenberg JJ, den Besten AP, de Kluyver E, van Nieuwstadt A, Wensvoort G, Moormann RJ. Molecular characterization of Lelystad virus. Vet Microbiol. 1997;55(1–4):197–202.

    Article  CAS  Google Scholar 

  23. Meulenberg JJ, Hulst MM, de Meijer EJ, Moonen PL, den Besten A, de Kluyver EP, Wensvoort G, Moormann RJ. Lelystad virus, the causative agent of porcine epidemic abortion and respiratory syndrome (PEARS), is related to LDV and EAV. Virology. 1993;192(1):62–72.

    Article  CAS  Google Scholar 

  24. Nelson EA, Christopher-Hennings J, Benfield DA. Serum immune responses to the proteins of porcine reproductive and respiratory syndrome (PRRS) virus. J Vet Diagn Invest. 1994;6(4):410–5.

    Article  CAS  Google Scholar 

  25. Overend C, Mitchell R, He D, Rompato G, Grubman MJ, Garmendia AE. Recombinant swine beta interferon protects swine alveolar macrophages and MARC-145 cells from infection with Porcine reproductive and respiratory syndrome virus. J Gen Virol. 2007;88(Pt 3):925–31.

    Article  CAS  Google Scholar 

  26. Sauer JD, Sotelo-Troha K, von Moltke J, Monroe KM, Rae CS, Brubaker SW, Hyodo M, Hayakawa Y, Woodward JJ, Portnoy DA, et al. The N-ethyl-N-nitrosourea-induced Goldenticket mouse mutant reveals an essential function of Sting in the in vivo interferon response to Listeria monocytogenes and cyclic dinucleotides. Infect Immun. 2011;79(2):688–94.

    Article  CAS  Google Scholar 

  27. Tian K, Yu X, Zhao T, Feng Y, Cao Z, Wang C, Hu Y, Chen X, Hu D, Tian X, et al. Emergence of fatal PRRSV variants: unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark. PLoS ONE. 2007;2:e526.

    Article  Google Scholar 

  28. Wang Y, Liang Y, Han J, Burkhart KM, Vaughn EM, Roof MB, Faaberg KS. Attenuation of porcine reproductive and respiratory syndrome virus strain MN184 using chimeric construction with vaccine sequence. Virology. 2008;371(2):418–29.

    Article  CAS  Google Scholar 

  29. Wang FX, Song N, Chen LZ, Cheng SP, Wu H, Wen YJ. Non-structural protein 2 of the porcine reproductive and respiratory syndrome (PRRS) virus: a crucial protein in viral pathogenesis, immunity and diagnosis. Res Vet Sci. 2013;95(1):1–7.

    Article  Google Scholar 

  30. Wang F-X, Yang B-C, Wen Y-J, Liu Z, Leng X, Shi X-C, Wang W, Li Z-G, Tan B, Chen L-Z, et al. Genomic characterization of porcine reproductive and respiratory syndrome virus TJM vaccine strain. Int Res J Microbiol. 2012;3(5):191–201.

    Google Scholar 

  31. Xiao Y, An TQ, Tian ZJ, Wei TC, Jiang YF, Peng JM, Zhou YJ, Cai XH, Tong GZ. The gene expression profile of porcine alveolar macrophages infected with a highly pathogenic porcine reproductive and respiratory syndrome virus indicates overstimulation of the innate immune system by the virus. Arch Virol. 2015;160(3):649–62.

    Article  CAS  Google Scholar 

  32. Xiao S, Jia J, Mo D, Wang Q, Qin L, He Z, Zhao X, Huang Y, Li A, Yu J, et al. Understanding PRRSV infection in porcine lung based on genome-wide transcriptome response identified by deep sequencing. PLoS ONE. 2010;5(6):e11377.

    Article  Google Scholar 

  33. Yang T, Zhang F, Zhai L, He W, Tan Z, Sun Y, Wang Y, Liu L, Ning C, Zhou W, et al. Transcriptome of Porcine PBMCs over Two Generations Reveals Key Genes and Pathways Associated with Variable Antibody Responses post PRRSV Vaccination. Sci Rep. 2018;8(1):2460.

    Article  Google Scholar 

Download references

Acknowledgements

This work was funded by High-level Talents Introduction Project of Inner Mongolia Agricultural University (NDYB2018-2), the Introducing Talents Scientific Research Project of Inner Mongolia Agricultural University ‘Research on prevention and control of herbivore animal diseases and biological products’ (NDGCC2016-22), and National Natural Science Foundation of China (NSFC)‘Molecular mechanism for synaptic recycling dysfunction induced by G protein of street rabies virus in primary mouse neural cells’(31572505). The study was also supported with Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, P.R China and Ruminant Animal Disease Diagnosis center, Inner Mongolia Agricultural University. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong-Jun Wen.

Ethics declarations

Conflict of interest

The authors declare no competing financial interests.

Additional information

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

Wang, FX., Liu, X., Wu, H. et al. Transcriptome sequencing analysis of porcine alveolar macrophages infected with PRRSV strains to elucidate virus pathogenicity and immune evasion strategies. VirusDis. 32, 559–567 (2021). https://doi.org/10.1007/s13337-021-00724-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13337-021-00724-0

Keywords

Navigation