Home Acta Virologica 2020 Acta Virologica Vol.64, No.1, p.78-87, 2020

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ISSN 0001-723X
E-ISSN 1336-2305

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Acta Virologica Vol.64, No.1, p.78-87, 2020

Title: Influenza A virus lacking the effector and C terminal domains of NS1 protein induces cytokines associated with high pathogenicity in mice
Author: L. TURIANOVÁ, V. LACHOVÁ, K. BEŇOVÁ, A. KOSTRÁBOVÁ, T. BETÁKOVÁ

Abstract: Non-structural NS1 protein of influenza A virus counters host antiviral defences by antagonizing the interferon response. The C-terminal effector domain suppresses the host response and is associated with the pathogenicity of the virus.  To better understand the regulatory role of the C-terminal domain, we used reverse genetics system to generate NS1-truncated virus (NS80) and compared the cytokine profiles in the lungs of mice infected with the NS80 mutant and with the control virus A/WSN/33 (WSN). The NS80 virus was attenuated and the viral titer in the lungs was about 25 times lower than viral titer of control A/WSN/33. Mice infected with NS80 virus exhibited more severe clinical symptoms and 2 mice died 6 days post infection. NS80 virus activated retinoic-inducible gene (RIG)-1-like receptor signaling pathway more strongly than control WSN virus and mice infected with NS80 virus exhibited a greater abundance and more diverse cytokine profile.  Infection with NS80 virus induced the expression of the following factors: pro-inflammatory cytokines (IL-1α, IL-1β, TNF-α, IL-16), interferons (IFN-α and IFN-ε), chemokines (CCL2, CCL11, CXCL1, CXCL5, CXCL10, CXCL11 and CXCL13), matrix metallopeptidase 9 (MMP-9), metallopeptidase inhibitor 1 (TIMP-1), macrophage colony-stimulating factor (M-CSF), and vascular cell adhesion protein 1 (VCAM-1). All these cytokines are associated with viral pathogenicity. Our data show that attenuation of the virus should not be directly linked with pathogenicity.

Keywords: influenza virus; NS1 protein; cytokines; interferon; pathogenicity
Published online: 11-Mar-2020
Year: 2020, Volume: 64, Issue: 1 Page From: 78, Page To: 87
doi:10.4149/av_2020_110


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