Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
Cathepsin B Protease Facilitates Chikungunya Virus Envelope Protein-Mediated Infection Via Endocytosis or Macropinocytosis
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DOI：
10.3390/v12070722
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发表时间：
2020-07-01
期刊：
影响因子：
4.7
通讯作者：
Kubo, Yoshinao
中科院分区：
文献类型：
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作者：
Izumida, Mai;Hayashi, Hideki;Kubo, Yoshinao
基孔肯雅病毒（CHIKV）是一种有包膜病毒，在开始复制周期之前进入宿主细胞并在内体内转运，其确切机制尚未阐明。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，表明这些病毒通过内体进入宿主细胞并需要内体酸化。尽管内体组织蛋白酶 B 是 MLV、埃博拉病毒和 SARS-CoV 感染所必需的，但其在 CHIKV 感染中的作用尚不清楚。我们的结果表明，内吞作用抑制剂可以减弱 293T 细胞中的 CHIKV 假型 MLV 载体感染，但不能减弱 TE671 细胞中的感染。相反，巨胞饮作用抑制剂可减弱 TE671 细胞中的 CHIKV 假型 MLV 载体感染，但不能减弱 293T 细胞中的感染，这表明 CHIKV 进入宿主细胞是通过内吞作用或巨胞饮作用发生的，具体取决于所使用的细胞系。组织蛋白酶 B 抑制剂和 shRNA 敲低可抑制 293T 和 TE671 细胞中的 CHIKV 假型 MLV 载体感染。这些结果表明，无论进入途径如何，组织蛋白酶 B 都会促进 CHIKV 感染。
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.