University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.
University of Leuven and Leuven University Hospitals, Department of Pathology, B-3000 Leuven, Belgium.
Antiviral Res. 2018 Jan;149:113-117. doi: 10.1016/j.antiviral.2017.09.016. Epub 2017 Sep 25.
Favipiravir (T-705) is a broad spectrum antiviral which has been approved in Japan for the treatment of severe influenza virus infections. We reported earlier that favipiravir inhibits the in vitro replication of CHIKV and protects against disease progression in CHIKV-infected immunodeficient mice. We here explored whether favipiravir is also able to inhibit CHIKV replication in the joints of mice either when treatment is initiated during the acute or during the chronic phase of the infection. To this end, C57BL/6J mice were infected with CHIKV in the left hind footpad and treatment with favipiravir (300 mg/kg/day, orally) was either given from day 0 to day 3 post-infection (p.i.) or from day 49 to day 55 p.i. In the untreated mice, viral RNA was still detectable in the joints up to 98 days p.i., yet no infectious viral particles were observed in these tissues. The 4 days treatment during the acute phase of the infection resulted in complete inhibition of systemic viral spread. As a consequence, no viral RNA was detected in the non-inoculated feet in contrast to the situation in the untreated control mice. When treatment was initiated at day 49 p.i., no significant reduction in viral RNA levels in joints were noted as compared to the untreated control. Interestingly, when attempting to amplify by RT-PCR material corresponding to virus genome from the chronic phase samples, some parts of the genome, such as the viral polymerase gene could not be amplified. Collectively, these results suggest that the viral RNA detected in the joints during the chronic phase is likely defective, which also explains the lack of effect of a viral replication inhibitor.
法匹拉韦（T-705）是一种广谱抗病毒药物，已在日本获得批准用于治疗严重流感病毒感染。我们之前报道过，法匹拉韦抑制 CHIKV 的体外复制，并可保护感染 CHIKV 的免疫缺陷小鼠免受疾病进展的影响。我们在此探讨了法匹拉韦是否也能抑制感染后急性或慢性期小鼠关节中的 CHIKV 复制。为此，我们将 C57BL/6J 小鼠用 CHIKV 感染左后脚掌垫，并给予法匹拉韦（300mg/kg/天，口服）治疗，从感染后第 0 天至第 3 天（p.i.）或从第 49 天至第 55 天 p.i.给药。在未治疗的小鼠中，病毒 RNA 可在关节中检测到高达 98 天 p.i.，但在这些组织中未观察到感染性病毒颗粒。在感染的急性期进行 4 天治疗可完全抑制系统性病毒扩散。因此，与未治疗的对照组相比，未接种的脚部未检测到病毒 RNA。当在第 49 天 p.i.开始治疗时，与未治疗的对照组相比，关节中病毒 RNA 水平没有明显降低。有趣的是，当试图从慢性期样本中用 RT-PCR 扩增对应病毒基因组的材料时，基因组的某些部分，如病毒聚合酶基因，无法扩增。总之，这些结果表明在慢性期关节中检测到的病毒 RNA 可能是缺陷的，这也解释了抗病毒复制抑制剂没有效果的原因。
