Table 1.

Ubiquitin-interfering viral proteins and the use of the ubiquitin–proteasome system by viruses of several families to complete their infection cycle.

Virus	Viral protein	Mechanism of action	References
Animal viruses
Rotavirus	NSP1	NSP1 prevents degradation of IκBα and maintains NFκB in its inhibited state by induction of β-TrCP degradation by UPS system	[42]
Human immunodeficiency virus type-1 (HIV-1)	Vpu	Vpu interacts with CD4 and β-TrCP triggering CD4 degradation by UPS system	[43]
Hepatitis E virus (HEV)	ORF2	ORF2 interacts with β-TrCP damaging SCF β-TrCP assembly. As a result, degradation of IκBα is inhibited and NFκB remains in its inhibited state	[44]
JC virus(JCV)	TAg	TAg interacts with β-TrCP and this interaction effect is unknown	[45]
Simian virus 5 (SV5) and type II Human parainfluenza virus (HPIV2)	V proteins	V proteins interact with CUL4 and DDB1 and this complex acts as an E3 ligase, leading to the degradation by UPS system of STAT proteins and key proteins that act in the type 1 IFN signaling	[46]
Myxoma virus	M150	Interacts with cullin and with p65 subunit of NFκB, triggering its degradation	[47]
Cowpox virus	CP77	Interacts with cullin and with p65 subunit of NFκB, triggering its degradation	[48]
Variola virus: Cowpox virus, Monkeypox virus, and Ectromelia virus	G1R	Interacts with cullin and with p105 subunit of NFκB, triggering its degradation	[49]
Poxvirus	proteins with BTB/Kelch domains	Interacts with CUL3 by BTB domain and with target protein by Kelch domain. The functions of these target proteins, however, is still unclear	[50]
Poxvirus	poxvirus APC/cyclosome regulator (PACR)	Interacts with APC/C proteins replacing the RING-H2 subunit APC11. PACR has no ligase activity, inhibiting the complex activity	[51]
Epstein-barr virus (EBV)	EBNA3C	Interferes in ubiquitination of p53 and MDM2, leading to degradation and stabilization of these proteins, respectively, inducing tumors; recruits SCFSKP2 complex to promote the degradation of the tumor suppressor P27 and Retinoblastoma (RB) proteins	[52–54]
Adenovirus type 5 (Ad5)	E1B-55K and E4-ORF6	Participate, with other proteins, of ubiquitin–ligase complex that directs P53 and other targets to degradation	[55–57]
Adenovirus type 5 (Ad5)	E1A	Interacts directly with components of the SCFFBW7 and undertakes its ubiquitin ligation activity by a mechanism not completely understood	[58]
Human papillomavirus (HPV)	E6 and E7	Interact with other proteins forming a complex that is able to ubiquitinate and degrade P53 and Retinoblastoma proteins, respectively	[59, 60]
Hepatitis B virus (HBV)	HBX	Increases the stability of c-MYC by inhibiting its SKP2-mediated degradation; Inhibits SCF-induced ubiquitination of the pituitary tumor-transforming gene 1 (PTTG1)-encoded protein by interaction with PTTG1 and the SCF ubiquitin–ligase complex	[61, 62]
herpesvirus KSHV	viral interferon-regulatory factor-3 (vIRF-3) protein	vIRF-3 enhances the transcription of c-MYC-regulated genes by interaction with SKP2. Interferes with P53 and NFκB activities during the infection process	[63–65]
herpesvirus KSHV	latency associated nuclear antigen	can compete with NOTCH for FBW7 binding, therefore, avoiding its degradation	[66]
Plant viruses
Geminivirus	C2	Interacts with CSN5, the catalytic subunit of the COP9 signalosome (CSN) complex, interfering in phytohormone regulation and suppressing responses mediated by jasmonate	[67]
Beet necrotic yellow vein virus (BNYVV)	P25	P25 binds to a host Kelch-type FBP and probably suppresses HR responses	[68, 69]
Nanovirus	CLINK	Acts as an FBP that is able to interact with RB proteins and SKP1 and enhances viral replication during nanovirus infection in a mechanism that probably inducing RB proteins degradation	[70]
Polerovirus	P0	It is able to interact with SKP2 and acts as silencing suppressor probably triggering AGO1 to degradation by UPS system. The action mechanism remains unclear	[71]
Potato virus X (PVX)	P25	Binds to AGO1, AGO2, AGO3 and AGO4 and triggers AGO1 to degradation in a proteasome	[72–74]