期刊
ACTA VIROLOGICA
卷 61, 期 1, 页码 48-55出版社
AEPRESS SRO
DOI: 10.4149/av_2017_01_48
关键词
influenza; T-705 (Favipiravir); TNF-alpha; cytokines; viral load
类别
资金
- Toyama Chemical Co. Ltd.
Influenza virus infection induces the production of various cytokines, which play important roles in the pathogenesis of infection. Among the cytokines induced by influenza, tumor necrosis factor a (TNF-alpha) production has been correlated with the severity of lung lesions. We investigated the effects of T-705 (Favipiravir, 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) on cytokine production due to influenza virus infection in vitro and in vivo, compared with oseltamivir or GS 4071, an active form of oseltamivir. TNF-alpha production in mouse macrophage-derived P388D1 cells infected with the influenza virus was lower following treatment with T-705 at concentrations of 0.3 to 100 mu g/ml than treatment with GS 4071 at the same concentrations. The effect of treatment with T-705 on the cytokine production induced by the influenza virus infection was investigated in mouse influenza virus infection model. At 48 h post-infection (p.i.) T-705 significantly suppressed the viral load in the lungs and TNF-alpha production in the airways of infected mice even when viral loads were high. Furthermore, T-705 suppressed only TNF-alpha production from the early phase of infection. In this study, T-705 showed the antiviral activity of reducing pulmonary viral load compared with oseltamivir, thereby suppressing the TNF-alpha production. This feature of T-705 is benefit against severe influenza infection.
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