Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression.
Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression.
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DOI：
10.1016/j.virol.2011.11.031
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发表时间：
2012-03-01
期刊：
影响因子：
3.7
通讯作者：
Pöhlmann S
中科院分区：
文献类型：
--
作者：
Gnirss K;Kühl A;Karsten C;Glowacka I;Bertram S;Kaup F;Hofmann H;Pöhlmann S
埃博拉病毒（EBOV）和马尔堡病毒（MARV）可引起严重的出血热。宿主细胞蛋白酶组织蛋白酶B和L激活扎伊尔埃博拉病毒糖蛋白（GP）进入细胞，并构成抗病毒干预的潜在靶标。然而，尚不清楚不同的EBOV物种和MARV是否同样依赖于组织蛋白酶B/L活性来感染细胞系和巨噬细胞（重要的病毒靶细胞）。在这里，我们表明组织蛋白酶B/L抑制剂显着减少了由所有EBOV物种的GP驱动的293 T细胞感染，而不依赖于II型跨膜丝氨酸蛋白酶TMPRSS 2，TMPRSS 2切割但未能激活EBOV-GP。类似地，组织蛋白酶B/L抑制剂阻断由不同EBOV-GP介导的巨噬细胞感染。相反，MARV-GP驱动的进入对组织蛋白酶B/L活性几乎没有依赖性。尽管如此，MARV-GP介导的进入被亮抑酶肽有效地阻断。这些结果表明，组织蛋白酶B/L促进EBOV的进入，而MARV可能利用迄今未鉴定的蛋白酶来激活GP。
Ebola (EBOV) and Marburg virus (MARV) cause severe hemorrhagic fever. The host cell proteases cathepsin B and L activate the Zaire ebolavirus glycoprotein (GP) for cellular entry and constitute potential targets for antiviral intervention. However, it is unclear if different EBOV species and MARV equally depend on cathepsin B/L activity for infection of cell lines and macrophages, important viral target cells. Here, we show that cathepsin B/L inhibitors markedly reduce 293T cell infection driven by the GPs of all EBOV species, independent of the type II transmembrane serine protease TMPRSS2, which cleaved but failed to activate EBOV-GPs. Similarly, a cathepsin B/L inhibitor blocked macrophage infection mediated by different EBOV-GPs. In contrast, MARV-GP-driven entry exhibited little dependence on cathepsin B/L activity. Still, MARV-GP-mediated entry was efficiently blocked by leupeptin. These results suggest that cathepsins B/L promote entry of EBOV while MARV might employ so far unidentified proteases for GP activation.
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影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
5.4
作者：
Hood, Chantelle L.;Abraham, Jonathan;Nabel, Gary J.
通讯作者：
Nabel, Gary J.
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
16.8
作者：
通讯作者：
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