Skip to main content
Log in

Role of zinc metalloprotease (ZMPSTE24) in porcine reproductive and respiratory syndrome virus (PRRSV) replication in vitro

  • Brief Report
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

The transmembrane zinc metalloprotease ZMPSTE24 works in cooperation with interferon-induced transmembrane protein 3 (IFITM3) to restrict entry of several enveloped viruses. We investigated the role of ZMPSTE24 in porcine reproductive and respiratory syndrome virus (PRRSV) replication. ZMPSTE24 overexpression significantly reduced PRRSV replication in MARC-145 cells. Interestingly, knockdown of endogenous ZMPSTE24 did not significantly impact virus replication. There was no significant difference in the percentage of PRRSV-positive cells and viral RNA copies at 3 hours postinfection (hpi) between cells transfected with ZMPSTE24-FLAG and the vector control. Our results suggest that ZMPSTE24 overexpression may restrict PRRSV replication at a post-entry step.

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

References

  1. Bailey CC, Zhong G, Huang IC, Farzan M (2014) IFITM-family proteins: the cell’s first line of antiviral defense. Annu Rev Virol 1:261–283

    Article  Google Scholar 

  2. Barrowman J, Michaelis S (2009) ZMPSTE24, an integral membrane zinc metalloprotease with a connection to progeroid disorders. Biol Chem 390:761–773

    Article  CAS  Google Scholar 

  3. Feeley EM, Sims JS, John SP, Chin CR, Pertel T, Chen LM, Gaiha GD, Ryan BJ, Donis RO, Elledge SJ, Brass AL (2011) IFITM3 inhibits influenza A virus infection by preventing cytosolic entry. PLoS Pathog 7:e1002337

    Article  CAS  Google Scholar 

  4. Fong LG, Ng JK, Meta M, Coté N, Yang SH, Stewart CL, Sullivan T, Burghardt A, Majumdar S, Reue K, Bergo MO, Young SG (2004) Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice. Proc Natl Acad Sci USA 101:18111–18116

    Article  CAS  Google Scholar 

  5. Fu B, Wang L, Li S, Dorf ME (2017) ZMPSTE24 defends against influenza and other pathogenic viruses. J Exp Med 214:919

    Article  CAS  Google Scholar 

  6. Guo R, Katz BB, Tomich JM, Gallagher T, Fang Y (2016) Porcine reproductive and respiratory syndrome virus utilizes nanotubes for intercellular spread. J Virol 90:5163–5175

    Article  CAS  Google Scholar 

  7. Kumar A, Kim JH, Ranjan P, Metcalfe MG, Cao W, Mishina M, Gangappa S, Guo Z, Boyden ES, Zaki S, York I, García-Sastre A, Shaw M, Sambhara S (2017) Influenza virus exploits tunneling nanotubes for cell-to-cell spread. Sci Rep 7:40360

    Article  CAS  Google Scholar 

  8. Lam JKW, Chow MYT, Zhang Y, Leung SWS (2015) siRNA versus miRNA as therapeutics for gene silencing. Mol Ther Nucleic Acids 4:e252

    Article  CAS  Google Scholar 

  9. Lei C, Yang J, Hu J, Sun X (2021) On the calculation of TCID(50) for quantitation of virus infectivity. Virol Sin 36:141–144

    Article  Google Scholar 

  10. Li S, Fu B, Wang L, Dorf ME (2017) ZMPSTE24 Is downstream effector of interferon-induced transmembrane antiviral activity. DNA Cell Biol 36:513–517

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. 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 

  13. Panasiuk M, Rychłowski M, Derewońko N, Bieńkowska-Szewczyk K (2018) Tunneling nanotubes as a novel route of cell-to-cell spread of herpesviruses. J Virol 92:e00090-18

    Article  Google Scholar 

  14. Schneider WM, Chevillotte MD, Rice CM (2014) Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol 32:513–545

    Article  CAS  Google Scholar 

  15. Smith S, Weston S, Kellam P, Marsh M (2014) IFITM proteins-cellular inhibitors of viral entry. Curr Opin Virol 4:71–77

    Article  CAS  Google Scholar 

  16. Stott RJ, Foster TL (2021) Inhibition of arenavirus entry and replication by the cell-intrinsic restriction factor ZMPSTE24 is enhanced by IFITM antiviral activity. bioRxiv:2021.2004.2012.439453

  17. Van Gorp H, Van Breedam W, Delputte PL, Nauwynck HJ (2009) The porcine reproductive and respiratory syndrome virus requires trafficking through CD163-positive early endosomes, but not late endosomes, for productive infection. Adv Virol 154:1939–1943

    Google Scholar 

  18. Zhang A, Duan H, Zhao H, Liao H, Du Y, Li L, Jiang D, Wan B, Wu Y, Ji P, Zhou E-M, Zhang G (2020) Interferon-induced transmembrane protein 3 is a virus-associated protein which suppresses porcine reproductive and respiratory syndrome virus replication by blocking viral membrane fusion. J Virol 94:e01350-e11320

    Article  CAS  Google Scholar 

  19. Zhang Q, Yoo D (2015) PRRS virus receptors and their role for pathogenesis. Vet Microbiol 177:229–241

    Article  CAS  Google Scholar 

Download references

Funding

This study was partly supported by Animal Health and Production and Animal Products: Animal Health and Disease (Grant no. 2021-67016-34460/project accession no. 1025717) from the USDA National Institute of Food and Agriculture (NIFA), and Hatch (SD00H660-19) and Hatch Multi State (SD00R656-16) from USDA NIFA and South Dakota Agricultural Experiment Station.

Author information

Authors and Affiliations

Authors

Contributions

XW designed the study, analyzed the data, and wrote the manuscript. PK conducted experiments, analyzed the results, and wrote the manuscript. SA conducted experiments and analyzed data. EN and SL provided reagents/analytic tools. MH contributed to confocal microscopy and analysis.

Corresponding author

Correspondence to Xiuqing Wang.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

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

Katwal, P., Aftab, S., Nelson, E. et al. Role of zinc metalloprotease (ZMPSTE24) in porcine reproductive and respiratory syndrome virus (PRRSV) replication in vitro. Arch Virol 167, 2281–2286 (2022). https://doi.org/10.1007/s00705-022-05529-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-022-05529-0

Navigation