Interleukin-15 mediates potent antiviral responses via an interferon-dependent mechanism

Y. Y. Foong; D. A. Jans; M. S. Rolph; M. E. Gahan; S. Mahalingam

doi:10.1016/j.virol.2009.07.030

Interleukin-15 mediates potent antiviral responses via an interferon-dependent mechanism

Y. Y. Foong, D. A. Jans, M. S. Rolph, M. E. Gahan, S. Mahalingam^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Interleukin-15 (IL-15) is a potent growth factor for activated T and natural killer (NK) cells, stimulator of memory T cells and plays an important role in viral immunity. To investigate mechanisms underlying the antiviral activity of IL-15, a recombinant vaccinia virus (rVV) encoding murine IL-15 (VV-IL-15) was constructed. Following infection of mice with VV-IL-15, virus titres in the ovaries were significantly reduced compared to mice infected with control VV. Growth of VV-IL-15 was also reduced in nude athymic mice, indicating the antiviral activity of IL-15 does not require T cells. Additionally, VV-IL-15 augmented the cytolytic activity of natural NK cells in the spleen and enhanced interferon (IFN) mRNA expression and transcription factors associated with IFN induction. Using knockout mice and antibody depletion studies, we showed for the first time that the control of VV-IL-15 replication in mice is dependent on NK cells and IFNs and, in their absence, the protective role of IL-15 is abolished.

Original language	English
Pages (from-to)	228-237
Number of pages	10
Journal	Virology
Volume	393
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2009.07.030
Publication status	Published - 25 Oct 2009

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title = "Interleukin-15 mediates potent antiviral responses via an interferon-dependent mechanism",

abstract = "Interleukin-15 (IL-15) is a potent growth factor for activated T and natural killer (NK) cells, stimulator of memory T cells and plays an important role in viral immunity. To investigate mechanisms underlying the antiviral activity of IL-15, a recombinant vaccinia virus (rVV) encoding murine IL-15 (VV-IL-15) was constructed. Following infection of mice with VV-IL-15, virus titres in the ovaries were significantly reduced compared to mice infected with control VV. Growth of VV-IL-15 was also reduced in nude athymic mice, indicating the antiviral activity of IL-15 does not require T cells. Additionally, VV-IL-15 augmented the cytolytic activity of natural NK cells in the spleen and enhanced interferon (IFN) mRNA expression and transcription factors associated with IFN induction. Using knockout mice and antibody depletion studies, we showed for the first time that the control of VV-IL-15 replication in mice is dependent on NK cells and IFNs and, in their absence, the protective role of IL-15 is abolished.",

keywords = "Interferons, Interleukin-15, NK cells, Recombinant vaccinia virus",

author = "Foong, {Y. Y.} and Jans, {D. A.} and Rolph, {M. S.} and Gahan, {M. E.} and S. Mahalingam",

year = "2009",

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doi = "10.1016/j.virol.2009.07.030",

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AU - Foong, Y. Y.

AU - Jans, D. A.

AU - Rolph, M. S.

AU - Gahan, M. E.

AU - Mahalingam, S.

PY - 2009/10/25

Y1 - 2009/10/25

N2 - Interleukin-15 (IL-15) is a potent growth factor for activated T and natural killer (NK) cells, stimulator of memory T cells and plays an important role in viral immunity. To investigate mechanisms underlying the antiviral activity of IL-15, a recombinant vaccinia virus (rVV) encoding murine IL-15 (VV-IL-15) was constructed. Following infection of mice with VV-IL-15, virus titres in the ovaries were significantly reduced compared to mice infected with control VV. Growth of VV-IL-15 was also reduced in nude athymic mice, indicating the antiviral activity of IL-15 does not require T cells. Additionally, VV-IL-15 augmented the cytolytic activity of natural NK cells in the spleen and enhanced interferon (IFN) mRNA expression and transcription factors associated with IFN induction. Using knockout mice and antibody depletion studies, we showed for the first time that the control of VV-IL-15 replication in mice is dependent on NK cells and IFNs and, in their absence, the protective role of IL-15 is abolished.

AB - Interleukin-15 (IL-15) is a potent growth factor for activated T and natural killer (NK) cells, stimulator of memory T cells and plays an important role in viral immunity. To investigate mechanisms underlying the antiviral activity of IL-15, a recombinant vaccinia virus (rVV) encoding murine IL-15 (VV-IL-15) was constructed. Following infection of mice with VV-IL-15, virus titres in the ovaries were significantly reduced compared to mice infected with control VV. Growth of VV-IL-15 was also reduced in nude athymic mice, indicating the antiviral activity of IL-15 does not require T cells. Additionally, VV-IL-15 augmented the cytolytic activity of natural NK cells in the spleen and enhanced interferon (IFN) mRNA expression and transcription factors associated with IFN induction. Using knockout mice and antibody depletion studies, we showed for the first time that the control of VV-IL-15 replication in mice is dependent on NK cells and IFNs and, in their absence, the protective role of IL-15 is abolished.

KW - Interferons

KW - Interleukin-15

KW - NK cells

KW - Recombinant vaccinia virus

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DO - 10.1016/j.virol.2009.07.030

M3 - Article

SN - 0042-6822

VL - 393

SP - 228

EP - 237

JO - Virology

JF - Virology

IS - 2

ER -

Interleukin-15 mediates potent antiviral responses via an interferon-dependent mechanism

Abstract

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