New world hantaviruses activate IFNλ production in type I IFN-deficient vero E6 cells

Joseph Prescott, Pamela Hall, Mariana Acuna-Retamar, Chunyan Ye, Marc G. Wathelet, Hideki Ebihara, Heinz Feldmann, Brian Hjelle

Research output: Contribution to journalArticle

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Abstract

Background Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS). These viruses induce a strong interferon-stimulated gene (ISG) response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN), rendering them unable to mount an efficient innate immune response to virus infection. Interferon λ, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner. Methodology/Principal Findings We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNλ. Three New World hantaviruses were similarly able to induce IFNλ expression in this cell line. The IFNλ contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7) without inducing ISGs. Conclusions/Significance Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNλ. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNλ production in these cells might increase their utility for virus propagation.

Original languageEnglish (US)
Article numbere11159
JournalPLoS One
Volume5
Issue number6
DOIs
StatePublished - Aug 11 2010
Externally publishedYes

Fingerprint

Hantavirus
Interferon Type I
Vero Cells
interferons
Viruses
Interferons
Virus Diseases
viruses
Cells
Hantavirus Infections
Innate Immunity
cells
cell lines
Cell Line
infection
Endothelial cells
Sin Nombre virus
endothelial cells
Endothelial Cells
RNA Helicases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Prescott, J., Hall, P., Acuna-Retamar, M., Ye, C., Wathelet, M. G., Ebihara, H., ... Hjelle, B. (2010). New world hantaviruses activate IFNλ production in type I IFN-deficient vero E6 cells. PLoS One, 5(6), [e11159]. https://doi.org/10.1371/journal.pone.0011159

New world hantaviruses activate IFNλ production in type I IFN-deficient vero E6 cells. / Prescott, Joseph; Hall, Pamela; Acuna-Retamar, Mariana; Ye, Chunyan; Wathelet, Marc G.; Ebihara, Hideki; Feldmann, Heinz; Hjelle, Brian.

In: PLoS One, Vol. 5, No. 6, e11159, 11.08.2010.

Research output: Contribution to journalArticle

Prescott, J, Hall, P, Acuna-Retamar, M, Ye, C, Wathelet, MG, Ebihara, H, Feldmann, H & Hjelle, B 2010, 'New world hantaviruses activate IFNλ production in type I IFN-deficient vero E6 cells', PLoS One, vol. 5, no. 6, e11159. https://doi.org/10.1371/journal.pone.0011159
Prescott, Joseph ; Hall, Pamela ; Acuna-Retamar, Mariana ; Ye, Chunyan ; Wathelet, Marc G. ; Ebihara, Hideki ; Feldmann, Heinz ; Hjelle, Brian. / New world hantaviruses activate IFNλ production in type I IFN-deficient vero E6 cells. In: PLoS One. 2010 ; Vol. 5, No. 6.
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abstract = "Background Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS). These viruses induce a strong interferon-stimulated gene (ISG) response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN), rendering them unable to mount an efficient innate immune response to virus infection. Interferon λ, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner. Methodology/Principal Findings We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNλ. Three New World hantaviruses were similarly able to induce IFNλ expression in this cell line. The IFNλ contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7) without inducing ISGs. Conclusions/Significance Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNλ. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNλ production in these cells might increase their utility for virus propagation.",
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