Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines.
Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines.
复制标题
DOI：
10.3389/fcimb.2018.00091
复制
发表时间：
2018
影响因子：
5.7
通讯作者：
Matsuyama T
中科院分区：
文献类型：
--
作者：
Hayashi H;Kubo Y;Izumida M;Takahashi E;Kido H;Sato K;Yamaya M;Nishimura H;Nakayama K;Matsuyama T
甲型流感病毒（IAV）中的胰蛋白酶样蛋白酶对血凝素（HA）的切割和激活是其成功感染和传播的必要先决条件。在宿主细胞中，一些跨膜丝氨酸蛋白酶如TMPRSS 2、TMPRSS 4和HAT，沿着血纤溶酶在血流中，已被报道将HA前体（HA 0）分子切割成其活性形式，HA 1和HA 2。一些胰蛋白酶原还可以增强IAV在某些细胞类型中的增殖（例如，大鼠成心肌细胞）。然而，该过程的精确激活机制尚不清楚，因为胰蛋白酶原的生理激活剂TMPRSS 15肠激酶的表达水平预期在这些细胞中非常低，十二指肠细胞除外。在这里，我们表明，至少有两种不同的肠激酶表达在各种人类细胞系，包括A549肺源性细胞。外源性肠激酶的表达能促进IAV在293T人肾细胞中的增殖，而敲低内源性肠激酶则抑制了IAV在A549细胞中的增殖。肠激酶能够增强HA在细胞中的加工，其在体外和IAV感染的细胞中也激活胰蛋白酶原。因此，我们得出结论，肠激酶通过激活胰蛋白酶原在人类细胞系中加工病毒HA而在IAV感染和增殖中起作用。
Cleavage and activation of hemagglutinin (HA) by trypsin-like proteases in influenza A virus (IAV) are essential prerequisites for its successful infection and spread. In host cells, some transmembrane serine proteases such as TMPRSS2, TMPRSS4 and HAT, along with plasmin in the bloodstream, have been reported to cleave the HA precursor (HA0) molecule into its active forms, HA1 and HA2. Some trypsinogens can also enhance IAV proliferation in some cell types (e.g., rat cardiomyoblasts). However, the precise activation mechanism for this process is unclear, because the expression level of the physiological activator of the trypsinogens, the TMPRSS15 enterokinase, is expected to be very low in such cells, with the exception of duodenal cells. Here, we show that at least two variant enterokinases are expressed in various human cell lines, including A549 lung-derived cells. The exogenous expression of these enterokinases was able to enhance the proliferation of IAV in 293T human kidney cells, but the proliferation was reduced by knocking down the endogenous enterokinase in A549 cells. The enterokinase was able to enhance HA processing in the cells, which activated trypsinogen in vitro and in the IAV-infected cells also. Therefore, we conclude that enterokinase plays a role in IAV infection and proliferation by activating trypsinogen to process viral HA in human cell lines.
登录
查看更多内容
影响因子：
6.7
作者：
Hatesuer B;Bertram S;Mehnert N;Bahgat MM;Nelson PS;Pöhlmann S;Schughart K
通讯作者：
Schughart K
影响因子：
88.1
作者：
Medina, Rafael A.;Garcia-Sastre, Adolfo
通讯作者：
Garcia-Sastre, Adolfo
影响因子：
56.9
作者：
Naldini, L;Blomer, U;Trono, D
通讯作者：
Trono, D
影响因子：
2.7
作者：
Indalao IL;Sawabuchi T;Takahashi E;Kido H
通讯作者：
Kido H
影响因子：
5.4
作者：
Kuehn, Nora;Bergmann, Silke;Schughart, Klaus
通讯作者：
Schughart, Klaus