Cell Division Control Protein 42 Interacts With Hepatitis E Virus Capsid Protein and Participates in Hepatitis E Virus Infection.
Cell Division Control Protein 42 Interacts With Hepatitis E Virus Capsid Protein and Participates in Hepatitis E Virus Infection.
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DOI：
10.3389/fmicb.2021.775083
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发表时间：
2021
影响因子：
5.2
通讯作者：
Zhou EM
中科院分区：
文献类型：
--
作者：
Fan M;Luo Y;Zhang B;Wang J;Chen T;Liu B;Sun Y;Nan Y;Hiscox JA;Zhao Q;Zhou EM
戊型肝炎病毒（HEV）在世界范围内引起人类的病毒性肝炎，而HEV物种的一个子集，禽HEV，在鸡中引起肝炎-脾肿大综合征。迄今为止，关于宿主蛋白与HEV相互作用并参与病毒感染的报道很少。先前的pull-down分析结合质谱分析表明，细胞分裂控制蛋白42（CDC 42），属于Rho GTdR家族的成员，被禽HEV衣壳蛋白拉下。我们证实了CDC 42与禽和哺乳动物HEV衣壳蛋白之间的直接相互作用。这种相互作用可以增加活性三磷酸鸟苷结合CDC 42状态（GTP-CDC 42）的量。随后，我们确定了CDC 42的表达和活性与宿主细胞中的HEV感染呈正相关。使用不同的CDC 42下游信号通路抑制剂，我们发现CDC 42-MRCK（CDC 42结合激酶）-非肌球蛋白IIA（NMIIA）途径参与裸禽和哺乳动物HEV感染，CDC 42相关p21激活激酶1（PAK 1）-NMIIA/Cofilin通路参与准包膜哺乳动物HEV感染和CDC 42-神经Wiskott-Aldrich综合征蛋白-肌动蛋白聚合蛋白Arp 2/3途径（CDC 42-（N-）WASP-Arp 2/3）途径参与了哺乳动物HEV的裸和准包膜感染。总的来说，这些结果首次证明了HEV衣壳蛋白可以直接与CDC 42结合，并且无包膜和准包膜HEV使用不同的CDC 42下游信号通路参与病毒感染。该研究为理解HEV在宿主细胞中的生命周期提供了新的见解，并为抗HEV感染的药物设计提供了新的靶点。
Hepatitis E Virus (HEV) causes viral hepatitis in humans worldwide, while a subset of HEV species, avian HEV, causes hepatitis-splenomegaly syndrome in chickens. To date, there are few reports on the host proteins interacting with HEV and being involved in viral infection. Previous pull-down assay combining mass spectrometry indicated that cell division control protein 42 (CDC42), a member belonging to the Rho GTPase family, was pulled down by avian HEV capsid protein. We confirmed the direct interaction between CDC42 and avian and mammalian HEV capsid proteins. The interaction can increase the amount of active guanosine triphosphate binding CDC42 state (GTP-CDC42). Subsequently, we determined that the expression and activity of CDC42 were positively correlated with HEV infection in the host cells. Using the different inhibitors of CDC42 downstream signaling pathways, we found that CDC42-MRCK (a CDC42-binding kinase)-non-myosin IIA (NMIIA) pathway is involved in naked avian and mammalian HEV infection, CDC42-associated p21-activated kinase 1 (PAK1)-NMIIA/Cofilin pathway is involved in quasi-enveloped mammalian HEV infection and CDC42-neural Wiskott-Aldrich syndrome protein-actin-polymerizing protein Arp2/3 pathway (CDC42-(N-)WASP-Arp2/3) pathway participates in naked and quasi-enveloped mammalian HEV infection. Collectively, these results demonstrated for the first time that HEV capsid protein can directly bind to CDC42, and non- and quasi-enveloped HEV use different CDC42 downstream signaling pathways to participate in viral infection. The study provided some new insights to understand the life cycle of HEV in host cells and a new target of drug design for combating HEV infection.
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影响因子：
64.8
作者：
Feng Z;Hensley L;McKnight KL;Hu F;Madden V;Ping L;Jeong SH;Walker C;Lanford RE;Lemon SM
通讯作者：
Lemon SM
影响因子：
19
作者：
Farhan H;Hsu VW
通讯作者：
Hsu VW
表皮生长因子受体调节丝切蛋白活性并促进传染性胃肠炎病毒进入肠上皮细胞
影响因子：
--
作者：
Hu W;Zhu L;Yang X;Lin J;Yang Q
通讯作者：
Yang Q
影响因子：
3.8
作者：
Haqshenas, G;Shivaprasad, HL;Meng, XJ
通讯作者：
Meng, XJ
影响因子：
5.4
作者：
Krautkrämer, E;Giese, SI;Fackler, OT
通讯作者：
Fackler, OT