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收稿日期:
2023-10-13
出版日期:
2024-06-06
发布日期:
2024-06-06
通讯作者:
桓晨
E-mail:lmsxsml@jlu.edu.cn
作者简介:
许明秀(1999-),女,山东省济南市人,在读硕士研究生,主要从事病毒与宿主相互关系方面的研究。
基金资助:
Received:
2023-10-13
Online:
2024-06-06
Published:
2024-06-06
Contact:
Chen HUAN
E-mail:lmsxsml@jlu.edu.cn
摘要:
F-Box蛋白家族是一类含有F-Box结构域的蛋白,与细胞S期激酶相关蛋白1(SKP1)、Cullin1、环框蛋白1(RBX1)共同形成SKP1-CUL1-F-Box(SCF)E3泛素连接酶复合物,该复合物介导底物发生泛素化修饰并经蛋白酶体途径降解。宿主F-Box蛋白在整个病毒感染周期中发挥关键作用。F-Box蛋白能够调控人类免疫缺陷病毒(HIV-1)和EB病毒(EBV)在内的多种RNA病毒和DNA病毒的复制,且调控机制均有所不同。在病毒进入宿主细胞后,宿主F-Box蛋白可以调控病毒复制过程中关键蛋白质的稳定性和降解,也可以增强病毒感染后宿主细胞的免疫应答,抑制病毒复制。部分F-Box蛋白能通过降解宿主限制因子、抑制病毒激活和干扰素信号通路等方式,协助病毒完成复制周期。病毒也可以通过编码含F-Box结构域的蛋白与宿主SKP1、Cullin1和RBX1蛋白结合, 降解宿主因子促进自身复制。 F-Box 蛋白调控在病毒感染过程中发挥的作用差异较大,一种F-Box蛋白能够调控多种病毒的复制,一种病毒也能被多种F-Box蛋白所调控,现从宿主F-Box蛋白和病毒F-Box蛋白角度,对F-Box蛋白在病毒感染过程中的作用机制进行综述,探讨以F-Box蛋白作为靶点,开发新型抗病毒药物的意义和潜在价值。
中图分类号:
许明秀, 桓晨. 宿主和病毒的F-Box蛋白在病毒感染过程中作用的研究进展[J]. 吉林大学学报(医学版), 2024, (): 1-10.
Mingxiu XU, Chen HUAN. Research progress in role of host and viral F-Box proteins in process of viral infection[J]. Journal of Jilin University(Medicine Edition), 2024, (): 1-10.
表1
宿主F-Box蛋白在病毒感染过程中的作用"
Virus classification | Virus | Host F-Box protein | Mechanism | Literature |
---|---|---|---|---|
RNA | HIV | FBXW1 | Degradation of phosphorylated Vpu and inhibition of NF-κB activity; binds to phosphorylated Vpu, and degrades CD4, enhances BST-2 ubiquitination, inhibits p53 phosphorylation,and promotes T cell apoptosis. Degrade ICAM-1 and promote viral replication | [ |
FBXO11 | Inhibition of HIV-1 LTR activity and inhibition of latent HIV-1 activation | [ | ||
FBXO1 | Degradation of Vif protein through K48 linked ubiquitin chains, reducing infectivity of progeny virions | [ | ||
FBXO34 | Promotion of ubiquitination degradation of hnRNP U, enhance HIV translation, and keep it in an activated state | [ | ||
VSV | FBXW7 | Promotion of ubiquitination degradation of SHP2, destroy SHP2/c-Cbl complex that can degrade RIG-I, stabilize RIG-I, and increase antiviral response of host cells | [ | |
FBXO21 | Promotion of polyubiquitination modification of ASK1 K29, enhance JNK and p38 signaling pathways, and promote production of pro-inflammatory cytokines and type Ⅰ interferon | [ | ||
IAV | FBXW1 | Decreasing of expression of NS1, thereby significantly reducing replication level of influenza virus | [ | |
FBXW7 | Ubiquitination degrades SHP2 and inhibits influenza A virus replication | [ | ||
FBXO45 | Mediating the polyubiquitination of IFNLR1 and reducing its protein stability | [ | ||
FBXO6 | Interacting with NLRX1 to reduce host antiviral response to influenza virus | [ | ||
PEDV | FBXW7 | Inhibiting PEDV infection by enhancing expression of endogenous RIG-I and TBK1 and activating host interferon signaling pathway | [ | |
RVFV | FBXO3 | NSs and FBXO3 are assembled into SCF complexes to degrade p62 and inhibit type Ⅰ interferon reaction | [ | |
FBXW11,FBXW1 | NSs recruit FBXW11 and FBXW1, degradation of PKR, disruption of PKR-mediated antiviral effects | [ | ||
HTLV‐1 | FBXO25 | HBZ inhibits polyubiquitination of HAX-2 protein and promotes HAX-3 expression by inhibiting the binding of HAX-1 and FBXO25 | [ | |
DNA | HSV-1 | FBXO2 | HSV-1 infection promotes shuttling of NFB42 between cytosol and nucleus, FBXO2 interacts with UL9, this interaction mediates export of UL9 protein from the nucleus to the cytosol, leading to its ubiquitination and degradation via 26S proteasome | [ |
EBV | FBXO2 | Interacting and degrading glycoprotein gB, reducing EBV infectivity | [ | |
EBV | SKP2 | 3C recruits SKP2 to cyclinA complex to promote ubiquitination degradation of p27 and ubiquitination of EB protein | [ | |
HCV | FBXL2 | NS5A protein forms complexes with IP3R3 and FBXL2, and promotes FBXL2 mediated degradation of IP3R3, promoting HBV infection | [ | |
KSHV | FBXW7 | FBXW7 increases ubiquitination degradation of ICN, and LANA can compete with ICN to bind to FBXW7 and save degradation of ICN | [ | |
SKP2 | vIRF-3 binds to SKP2 ubiquitin ligase, stimulates ubiquitination and transcriptional activity of c-Myc, and promotes tumorigenesis | [ | ||
Adenovirus | FBW7 | E1A interacts with RR1/RBX1 to inhibit FBW7 ubiquitination, reduce endogenous FBW7 degradation, and promote cancer cell proliferation | [ |
表2
病毒F-Box蛋白在病毒感染过程中的作用机制"
Virus classification | Viral F-Box protein | Mechanism | Literature |
---|---|---|---|
ECTV | EVM00,EVM00, EVM15,EVM165 | Interacting with SKP1, Cullin1, and ROC1 to form SCF complexes, exercising ubiquitination function and inhibiting TNF-α and IL-1β Stimulating IκB-a degradation and p65 nuclear translocation, inhibiting activation of NF- κB | [ |
VV | C9 | Recognition of IFITs and degradation of IFITs through proteasome pathway affect antiviral activity of host | [ |
vIRD | Promotion of RIPK3 ubiquitin degradation and promotion of viral replication | [ | |
ORFV | ORF00,ORF12, ORF12,ORF128 | Suppressing of degradation of p-IκBα protein, preventing nuclear translocation of p65, and inhibiting host activation of NF-κB signaling pathway | [ |
Megavirus | FNIP | Interacting with host Rap1B and Rap7A to form SCF complexes, promoting degradation of Rap1B and Rap7A | [ |
Baculovirus | LEF-7 | Suppressing of key regions of phosphorylated H2AX, enhance release of late stage genes of virus, and increase virus replication | [ |
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