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

doi:10.13481/j.1671-587X.20250130

Abstract

Abstract:

The F-Box protein family is one kind of proteins containing the F-Box domain， which are together with S-phase kinase associated protein 1（SKP1）， Cullin1， and ring box protein 1（RBX1） to form the SKP1-CUL1-F-Box（SCF） E3 ubiquitin ligase complex； this complex mediates substrate ubiquitination modification and subsequent degradation via the proteasome pathway. The host F-Box protein plays an important role during the whole viral infection. The F-Box protein can regulate the replication of various RNA virus and DNA virus such as human immunodeficiency virus（HIV） and epstein-barrvirus（EB）， and the regulation mechanisms are different. After the virus enters the host cells， the host F-Box protein can regulate the stability and degradation of the key proteins during virus replication， enhance the immune response of host cells after virus infection， and inhibit the virus replication. Some F-Box proteins can assist the virus in completing the replication cycle by degrading the host restriction factors and inhibiting the virus activation and the interferon signaling pathway. The viruses also degradade the host factors and promote their own replication by encoding proteins containing the F-Box domain to bind to host SKP1， Cullin1， and RBX1 proteins. There are significant differences in the role of F-Box protein regulation during virus infection； one F-Box protein can regulate the replication of multiple viruses， and one virus can also be regulated by multiple F-Box proteins. This study systematically reviews the role of F-Box proteins in the process of viral infection from the perspectives of host F-Box proteins and viral F-Box proteins， and further explores the significance and potential value of F-Box proteins as targets for developing novel antiviral drugs.

Key words: F-Box protein, Virus, Ubiquitin-proteasome pathway, S-phase kinase-associated protein 1, Ring box protein 1

CLC Number:

R373

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), 2025, 51(1): 245-254.

Figures/Tables 2

Tab.1

Role of host F-Box protein in process of viral infection"

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	[27,35-40]
		FBXO11	Inhibition of HIV-1 LTR activity and inhibition of latent HIV-1 activation	[20]
		FBXO1	Degradation of Vif protein through K48 linked ubiquitin chains, reducing infectivity of progeny virions	[23]
		FBXO34	Promotion of ubiquitination degradation of hnRNP U, enhance HIV translation, and keep it in an activated state	[43]
	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	[31]
	VSV	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	[22]
	IAV	FBXW1	Decreasing of expression of NS1, thereby significantly reducing replication level of influenza virus	[28]
		FBXW7	Ubiquitination degrades SHP2 and inhibits influenza A virus replication	[30]
		FBXO45	Mediating the polyubiquitination of IFNLR1 and reducing its protein stability	[47]
		FBXO6	Interacting with NLRX1 to reduce host antiviral response to influenza virus	[46]
	PEDV	FBXW7	Inhibiting PEDV infection by enhancing expression of endogenous RIG-I and TBK1 and activating host interferon signaling pathway	[32]
	RVFV	FBXO3	NSs and FBXO3 are assembled into SCF complexes to degrade p62 and inhibit type Ⅰ interferon reaction	[45]
	RVFV	FBXW11，FBXW1	NSs recruit FBXW11 and FBXW1, degradation of PKR, disruption of PKR-mediated antiviral effects	[41-42]
	HTLV‐1	FBXO25	HBZ inhibits polyubiquitination of HAX-2 protein and promotes HAX-3 expression by inhibiting the binding of HAX-1 and FBXO25	[53]
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	[33-34]
	EBV	FBXO2	Interacting and degrading glycoprotein gB, reducing EBV infectivity	[13]
	EBV	SKP2	3C recruits SKP2 to cyclinA complex to promote ubiquitination degradation of p27 and ubiquitination of EB protein	[51-52]
	HCV	FBXL2	NS5A protein forms complexes with IP3R3 and FBXL2, and promotes FBXL2 mediated degradation of IP3R3, promoting HBV infection	[44]
	KSHV	FBXW7	FBXW7 increases ubiquitination degradation of ICN, and LANA can compete with ICN to bind to FBXW7 and save degradation of ICN	[48]
	KSHV	SKP2	vIRF-3 binds to SKP2 ubiquitin ligase, stimulates ubiquitination and transcriptional activity of c-Myc, and promotes tumorigenesis	[49]
	Adenovirus	FBW7	E1A interacts with RR1/RBX1 to inhibit FBW7 ubiquitination, reduce endogenous FBW7 degradation, and promote cancer cell proliferation	[50]

Tab.1

Tab.2

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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	[58-60]
VV	C9	Recognition of IFITs and degradation of IFITs through proteasome pathway affect antiviral activity of host	[54]
VV	vIRD	Promotion of RIPK3 ubiquitin degradation and promotion of viral replication	[55]
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	[61]
Megavirus	FNIP	Interacting with host Rap1B and Rap7A to form SCF complexes, promoting degradation of Rap1B and Rap7A	[56]
Baculovirus	LEF-7	Suppressing of key regions of phosphorylated H2AX, enhance release of late stage genes of virus, and increase virus replication	[57]

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Research progress in role of host and viral F-Box proteins in process of viral infection

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