TY - JOUR
T1 - Interleukin-15 mediates potent antiviral responses via an interferoj-dependent mechanism
AU - Foong, Y
AU - Jans, D
AU - Rolph, Michael
AU - Gahan, Michelle
AU - Mahalingam, Suresh
PY - 2009
Y1 - 2009
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.
U2 - 10.1016/j.virol.2009.07.030
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 -
