Gamma-irradiated influenza virus uniquely induces IFN-I mediated lymphocyte activation independent of the TLR7/MyD88 pathway

• Published in: PloS one 2011-10, Vol.6 (10), p.e25765
• Main Authors: Furuya, Yoichi, Chan, Jennifer, Wan, En-Chi, Koskinen, Aulikki, Diener, Kerrilyn R, Hayball, John D, Regner, Matthias, Müllbacher, Arno, Alsharifi, Mohammed
• Format: Article
• Language: English
• Subjects: Activation; Animals; Biology; CD25 antigen; CD69 antigen; CD86 antigen; Cell activation; Cell Line; Cell surface; Cricetinae; Cytotoxicity; Dogs; Female; Gamma Rays; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Influenza; Influenza A; Influenza A Virus, H1N1 Subtype - metabolism; Influenza A Virus, H1N1 Subtype - physiology; Influenza A Virus, H1N1 Subtype - radiation effects; Influenza A Virus, H3N2 Subtype - metabolism; Influenza A Virus, H3N2 Subtype - physiology; Influenza A Virus, H3N2 Subtype - radiation effects; Interferon; Interferon Type I - biosynthesis; Interferon Type I - metabolism; Ionizing radiation; Irradiated; Lymphocytes; Lymphocytes - cytology; Lymphocytes - metabolism; Lymphocytes - virology; Lymphocytes T; Medicine; Membrane Glycoproteins - metabolism; Mice; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; Neuraminidase - metabolism; Radiation; Receptors; Signal Transduction; Signaling; T cell receptors; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Cytotoxic - virology; TLR7 protein; Toll-Like Receptor 7 - metabolism; Toll-like receptors; U.V. radiation; Ultraviolet radiation; Vaccines; Viral infections; Virus Activation - radiation effects; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0025765

We have shown previously in mice, that infection with live viruses, including influenza/A and Semliki Forest virus (SFV), induces systemic partial activation of lymphocytes, characterized by cell surface expression of CD69 and CD86, but not CD25. This partial lymphocytes activation is mediated by type-I interferons (IFN-I). Importantly, we have shown that γ-irradiated SFV does not induce IFN-I and the associated lymphocyte activation. Here we report that, in contrast to SFV, γ-irradiated influenza A virus elicits partial lymphocyte activation in vivo. Furthermore, we show that when using influenza viruses inactivated by a variety of methods (UV, ionising radiation and formalin treatment), as well as commercially available influenza vaccines, only γ-irradiated influenza virus is able to trigger IFN-I-dependent partial lymphocyte activation in the absence of the TLR7/MyD88 signalling pathways. Our data suggest an important mechanism for the recognition of γ-irradiated influenza vaccine by cytosolic receptors, which correspond with the ability of γ-irradiated influenza virus to induce cross-reactive and cross-protective cytotoxic T cell responses.