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Species specificity of type III interferon activity and development of a sensitive luciferase-based bioassay for quantitation of mouse interferon-λ

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Abstract
The type III interferon (IFN-lambda) family includes 4 IFN-lambda subtypes in man. In the mouse, only the genes coding for IFN-lambda 2 and -lambda 3 are present. Unlike mouse and human type I IFNs (IFN-alpha/beta), which exhibit strong species specificity, type III IFNs were reported to act in a cross-specific manner. We reexamined the cross-specificity and observed that mouse and human IFN-lambda exhibit some species specificity, although much less than type I IFNs. Mouse IFN-lambda 3 displayed clear species specificity, being 25-fold less active in human cells than the closely related mouse IFN-lambda 2. This specificity likely depends on amino acids in alpha helices A and F that diverged from other IFN-lambda sequences. Human IFN-lambda 4, in contrast, retained high activity in mouse cells. We next developed a firefly luciferase-based reporter cell line, named Fawa-lambda-luc, to detect IFN-lambda in biological fluids with high specificity and sensitivity. Fawa-lambda-luc cells, derived from mouse epithelial cells that are responsive to IFN-lambda, were made nonresponsive to type I IFNs by inactivation of the Ifnar2 gene and strongly responsive to IFN-lambda by overexpression of the mouse IFNLR1. This bioassay was as sensitive as a commercially available enzyme-linked immunosorbent assay in detecting mouse IFN-lambda in cell culture supernatant, as well as in serum and bronchoalveolar lavage samples of virus-infected mice. The assay also enabled the sensitive detection of human IFN-lambda activity, including that of the divergent IFN-lambda 4 with a bias, however, due to variable activity of IFN-lambda subtypes.
Keywords
species-specific activity, cross-species activity, IFN-lambda receptor, IFN-lambda, type I IFN, antiviral, cytokine, respiratory syncytial virus, IFN-LAMBDA, FUNCTIONAL-ANALYSIS, ANTIVIRAL ACTIVITY, RECEPTOR, VIRUS, INFLAMMATION, PROTECTION, IL-29

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Citation

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Chicago
Jacobs, Sophie, Fanny Wavreil, Bert Schepens, Hans Henrik Gad, Rune Hartmann, Joana Rocha-Pereira, Johan Neyts, Xavier Saelens, and Thomas Michiels. 2018. “Species Specificity of Type III Interferon Activity and Development of a Sensitive Luciferase-based Bioassay for Quantitation of Mouse Interferon-λ.” Journal of Interferon and Cytokine Research 38 (11): 469–479.
APA
Jacobs, Sophie, Wavreil, F., Schepens, B., Gad, H. H., Hartmann, R., Rocha-Pereira, J., Neyts, J., et al. (2018). Species specificity of type III interferon activity and development of a sensitive luciferase-based bioassay for quantitation of mouse interferon-λ. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 38(11), 469–479.
Vancouver
1.
Jacobs S, Wavreil F, Schepens B, Gad HH, Hartmann R, Rocha-Pereira J, et al. Species specificity of type III interferon activity and development of a sensitive luciferase-based bioassay for quantitation of mouse interferon-λ. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH. 2018;38(11):469–79.
MLA
Jacobs, Sophie et al. “Species Specificity of Type III Interferon Activity and Development of a Sensitive Luciferase-based Bioassay for Quantitation of Mouse Interferon-λ.” JOURNAL OF INTERFERON AND CYTOKINE RESEARCH 38.11 (2018): 469–479. Print.
@article{8583715,
  abstract     = {The type III interferon (IFN-lambda) family includes 4 IFN-lambda subtypes in man. In the mouse, only the genes coding for IFN-lambda 2 and -lambda 3 are present. Unlike mouse and human type I IFNs (IFN-alpha/beta), which exhibit strong species specificity, type III IFNs were reported to act in a cross-specific manner. We reexamined the cross-specificity and observed that mouse and human IFN-lambda exhibit some species specificity, although much less than type I IFNs. Mouse IFN-lambda 3 displayed clear species specificity, being 25-fold less active in human cells than the closely related mouse IFN-lambda 2. This specificity likely depends on amino acids in alpha helices A and F that diverged from other IFN-lambda sequences. Human IFN-lambda 4, in contrast, retained high activity in mouse cells. We next developed a firefly luciferase-based reporter cell line, named Fawa-lambda-luc, to detect IFN-lambda in biological fluids with high specificity and sensitivity. Fawa-lambda-luc cells, derived from mouse epithelial cells that are responsive to IFN-lambda, were made nonresponsive to type I IFNs by inactivation of the Ifnar2 gene and strongly responsive to IFN-lambda by overexpression of the mouse IFNLR1. This bioassay was as sensitive as a commercially available enzyme-linked immunosorbent assay in detecting mouse IFN-lambda in cell culture supernatant, as well as in serum and bronchoalveolar lavage samples of virus-infected mice. The assay also enabled the sensitive detection of human IFN-lambda activity, including that of the divergent IFN-lambda 4 with a bias, however, due to variable activity of IFN-lambda subtypes.},
  author       = {Jacobs, Sophie and Wavreil, Fanny and Schepens, Bert and Gad, Hans Henrik and Hartmann, Rune and Rocha-Pereira, Joana and Neyts, Johan and Saelens, Xavier and Michiels, Thomas},
  issn         = {1079-9907},
  journal      = {JOURNAL OF INTERFERON AND CYTOKINE RESEARCH},
  language     = {eng},
  number       = {11},
  pages        = {469--479},
  title        = {Species specificity of type III interferon activity and development of a sensitive luciferase-based bioassay for quantitation of mouse interferon-\ensuremath{\lambda}},
  url          = {http://dx.doi.org/10.1089/jir.2018.0066},
  volume       = {38},
  year         = {2018},
}

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