Ivermectin inhibits porcine reproductive and respiratory syndrome virus in cultured porcine alveolar macrophages

Ivermectin inhibits porcine reproductive and respiratory syndrome virus in cultured porcine... Porcine reproductive and respiratory syndrome virus (PRRSV) is a devastating viral pathogen of swine that causes huge financial losses in the pig industry worldwide. Ivermectin is known to be a potent inhibitor of importin α/β-mediated nuclear transport and exhibits antiviral activity towards several RNA viruses by blocking the nuclear trafficking of viral proteins. Although PRRSV replication occurs exclusively in the cytoplasm of infected cells, the nucleocapsid (N) protein has been shown to distinctly localize in the nucleus and nucleolus throughout infection. Here, we sought to assess whether ivermectin suppresses PRRSV replication in cultured porcine alveolar macrophage (PAM) cells and to investigate the effect of ivermectin on the subcellular localization of the PRRSV N protein. Our data demonstrate that ivermectin treatment inhibits PRRSV infection in PAM-pCD163 cells in a dose-dependent manner. The antiviral activity of ivermectin on PRRSV replication was most effective when cells were treated during the early stage of infection. Treatment of PRRSV-infected cells with ivermectin significantly suppressed viral RNA synthesis, viral protein expression, and progeny virus production. However, immunofluorescence and cell fractionation assays revealed that ivermectin was incapable of disrupting the nuclear localization of the N protein, both in PRRSV-infected PAM-pCD163 cells and in PAM cells stably expressing the PRRSV N protein. This finding suggests that an alternative mechanism of action accounts for the ability of ivermectin to diminish PRRSV replication. Taken together, our results suggest that ivermectin is an invaluable therapeutic or preventative agent against PRRSV infection. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Ivermectin inhibits porcine reproductive and respiratory syndrome virus in cultured porcine alveolar macrophages

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Publisher
Springer Journals
Copyright
Copyright © 2016 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-015-2653-2
Publisher site
See Article on Publisher Site

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is a devastating viral pathogen of swine that causes huge financial losses in the pig industry worldwide. Ivermectin is known to be a potent inhibitor of importin α/β-mediated nuclear transport and exhibits antiviral activity towards several RNA viruses by blocking the nuclear trafficking of viral proteins. Although PRRSV replication occurs exclusively in the cytoplasm of infected cells, the nucleocapsid (N) protein has been shown to distinctly localize in the nucleus and nucleolus throughout infection. Here, we sought to assess whether ivermectin suppresses PRRSV replication in cultured porcine alveolar macrophage (PAM) cells and to investigate the effect of ivermectin on the subcellular localization of the PRRSV N protein. Our data demonstrate that ivermectin treatment inhibits PRRSV infection in PAM-pCD163 cells in a dose-dependent manner. The antiviral activity of ivermectin on PRRSV replication was most effective when cells were treated during the early stage of infection. Treatment of PRRSV-infected cells with ivermectin significantly suppressed viral RNA synthesis, viral protein expression, and progeny virus production. However, immunofluorescence and cell fractionation assays revealed that ivermectin was incapable of disrupting the nuclear localization of the N protein, both in PRRSV-infected PAM-pCD163 cells and in PAM cells stably expressing the PRRSV N protein. This finding suggests that an alternative mechanism of action accounts for the ability of ivermectin to diminish PRRSV replication. Taken together, our results suggest that ivermectin is an invaluable therapeutic or preventative agent against PRRSV infection.

Journal

Archives of VirologySpringer Journals

Published: Feb 1, 2016

References

  • The PRRSV replicase: exploring the multifunctionality of an intriguing set of nonstructural proteins
    Fang, Y; Snijder, EJ
  • Regulation of nucleocytoplasmic trafficking of viral proteins: an integral role in pathogenesis?
    Fulcher, AJ; Jans, DA
  • Immunopathogenesis of porcine reproductive and respiratory syndrome in the respiratory tract of pigs
    Gómez-Laguna, J; Salguero, FJ; Pallarés, FJ; Carrasco, L
  • Porcine reproductive and respiratory syndrome virus replication is suppressed by inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway
    Lee, YJ; Lee, C
  • Generation of a porcine alveolar macrophage cell line for the growth of porcine reproductive and respiratory syndrome virus
    Lee, YJ; Park, CK; Nam, E; Kim, SH; Lee, OS; Lee, DS; Lee, C
  • Porcine reproductive and respiratory syndrome virus: an update on an emerging and re-emerging viral disease of swine
    Lunney, JK; Benfield, DA; Rowland, RR
  • The localization of porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus of infected cells and identification of a potential nucleolar localization signal sequence
    Rowland, RR; Kervin, R; Kuckleburg, C; Sperlich, A; Benfield, DA

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