Chikungunya virus (CHIKV) is an enveloped virus that enters host cells and transits within the endosomes before starting its replication cycle, the precise mechanism of which is yet to be elucidated. Endocytosis and endosome acidification inhibitors inhibit infection by CHIKV, murine leukemia virus (MLV), or SARS-coronavirus, indicating that these viral entries into host cells occur through endosomes and require endosome acidification. Although endosomal cathepsin B protease is necessary for MLV, Ebola virus, and SARS-CoV infections, its role in CHIKV infection is unknown. Our results revealed that endocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in 293T cells but not in TE671 cells. In contrast, macropinocytosis inhibitors attenuated CHIKV-pseudotyped MLV vector infection in TE671 cells but not in 293T cells, suggesting that CHIKV host cell entry occurs via endocytosis or macropinocytosis, depending on the cell lines used. Cathepsin B inhibitor and knockdown by an shRNA suppressed CHIKV-pseudotyped MLV vector infection both in 293T and TE671 cells. These results show that cathepsin B facilitates CHIKV infection regardless of the entry pathway.

中文翻译：

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组织蛋白酶B蛋白酶通过胞吞作用或巨胞饮作用促进基孔肯雅病毒包膜蛋白介导的感染。

基孔肯雅热病毒（CHIKV）是一种包膜病毒，在开始其复制周期之前会进入宿主细胞并在核内体中传播，其确切机制尚待阐明。内吞作用和内体酸化抑制剂可抑制CHIKV，鼠白血病病毒（MLV）或SARS冠状病毒的感染，表明这些病毒进入宿主细胞的过程是通过内体发生的，需要内体酸化。尽管MLV，埃博拉病毒和SARS-CoV感染需要内体组织蛋白酶B蛋白酶，但其在CHIKV感染中的作用尚不清楚。我们的结果表明，内吞抑制剂可减弱293T细胞中CHIKV假型MLV载体的感染，但不能减弱TE671细胞中的感染。相比之下，巨胞饮抑制剂可减弱TE671细胞中CHIKV假型MLV载体的感染，但不能减弱293T细胞中的感染，提示CHIKV宿主细胞进入是通过内吞作用或巨胞饮作用发生的，这取决于所使用的细胞系。组织蛋白酶B抑制剂和shRNA的敲低抑制了293T和TE671细胞中CHIKV假型MLV载体的感染。这些结果表明，与进入途径无关，组织蛋白酶B促进CHIKV感染。