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.

Favipiravir（T-705）是广谱抗病毒药物，已在日本批准用于治疗严重的流感病毒感染。我们之前曾报道过，favipiravir会抑制体外CHIKV的复制并保护其免受CHIKV感染的免疫缺陷小鼠的疾病进展。我们在这里探讨了当在感染的急性期或慢性期开始治疗时，favipiravir是否还能够抑制小鼠关节中的CHIKV复制。为此，C57BL / 6J小鼠在左后足垫感染了CHIKV，并于感染后第0天到第3天或从感染后第49天开始给予favipiravir（300 mg / kg /天，口服）治疗到感染后第55天（第55天），在未经治疗的小鼠中，直到感染后第98天仍可在关节中检测到病毒RNA，但在这些组织中未观察到感染性病毒颗粒。感染急性期的4天治疗导致系统性病毒传播的完全抑制。作为结果，与未治疗的对照小鼠相比，在未接种的脚中未检测到病毒RNA。当在感染后第49天开始治疗时，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，当尝试通过RT-PCR从慢性期样本中扩增出与病毒基因组相对应的材料时，基因组的某些部分（如病毒聚合酶基因）无法被扩增。总的来说，这些结果表明在慢性期在关节中检测到的病毒RNA可能是有缺陷的，这也解释了病毒复制抑制剂的作用不足。与未处理的对照相比，没有观察到关节中病毒RNA水平的显着降低。有趣的是，当尝试通过RT-PCR从慢性期样本中扩增出与病毒基因组相对应的材料时，基因组的某些部分（如病毒聚合酶基因）无法被扩增。总的来说，这些结果表明在慢性期在关节中检测到的病毒RNA可能是有缺陷的，这也解释了缺乏病毒复制抑制剂的作用。与未处理的对照相比，没有观察到关节中病毒RNA水平的显着降低。有趣的是，当尝试通过RT-PCR从慢性期样本中扩增出与病毒基因组相对应的材料时，基因组的某些部分（如病毒聚合酶基因）无法被扩增。总的来说，这些结果表明在慢性期在关节中检测到的病毒RNA可能是有缺陷的，这也解释了缺乏病毒复制抑制剂的作用。