Viral manipulation of cellular protein conjugation pathways: The SUMO lesson

Table 1 Viral life cycle and small ubiquitin-like modifier pathway

Virus	Protein	Interaction with SUMO	Proposed impact on viral or cellular activity	Ref.
Chicken embryo lethal orphan Adenovirus	Gam1	Overall SUMOylation decrease through SAE1/2 degradation and reduced Ubc9 expression	Cellular transcriptional activation	[49,50]
			PML-NBs dispersion	[51]
		Interference with HDAC1 SUMOylation	Cellular transcriptional activation	[51]
Geminivirus	AL1	Promotes SUMOylation of selected host factors	Viral replication	[57,58]
Adenovirus	E1B-55K	E3 ligase SUMO-1 specific	Regulator of cell cycle and apoptosis	[59,60]
		SUMOylated	Cellular transformation	[63]
			Interaction with PML-NBs	[62,64]
Kaposi’s sarcoma-associated herpesvirus	K-bZip	E3 ligase SUMO-2/3 specific	Regulator of cell cycle and apoptosis	[66]
		SUMOylated	Cellular transcriptional repression	[65,66]
	K-Rta	E3 ubiquitin ligase activity against SUMOylated proteins	PML-NBs dispersion	[119]
Vaccinia	E3	SUMOylated	Regulator of apoptosis	[69]
	A40R	SUMOylated	Viral replication	[74]
Bovine papillomavirus	E1	SUMOylated	Viral replication	[71,72]
Human papillomavirus	L2	SUMOylated	Viral capsid assembly	[93]
		Increase in cellular SUMO 2/3 conjugation		[93]
Moloney murine leukemia	CA	SUMOylated	Viral replication	[75]
Influenza A	NS1	SUMOylated	Viral replication	[78]
Cytomegalovirus	IE1	SUMOylated	Viral replication	[80,81]
		Interaction with selected host factors	PML dispersion	[123]
		SUMOylated
	IE2	Interaction with SUMOylated proteins	Viral replication	[82]
		SUMOylated	Viral replication	[83]
	UL44	Interaction with Ubc9	Viral replication	[84]
Epstein-Barr	BZLF1	SUMOylated	Reactivation of latent infections	[85,86,88]
	Rta	SUMOylated	Reactivation of latent infections	[89]
	BGLF4	Interaction with SUMOylated proteins	Viral replication and reactivation of latent infections	[91]
			PML-NBs dispersion
Hantaan	NP	Interaction with Ubc9 and SUMO-1	Virus assembly	[95,96]
Mason-Pfizer; human immunodeficiency	Gag	Interaction with Ubc9	Virus assembly	[97]
				[98-100]
Influenza A	M1	SUMOylated	Virus assembly	[102,103]
Ebola Zaire	VP35	Promotes SUMOylation of selected host factors	IFN inhibition	[109,111]
Herpes simplex type-1	ICP0	E3 ubiquitin ligase activity against SUMOylated proteins	PML-NBs dispersion	[115-117]
Varicella zoster	ORF61	Interaction with SUMOylated proteins	PML-NBs dispersion	[120,121]
Encephalomyocarditis	3C	Interaction with selected host factors	PML degradation	[122]

The table schematizes known viral proteins interacting with the small ubiquitin-like modifier (SUMO) pathway, with a brief description of their relationship with the SUMOylation machinery and the proposed biological outcome. References are also reported (see text for further details). SAE: SUMO-activating enzyme subunit; HDAC: Histone deacetylase; PML-NBs: ProMyelocyticLeukaemia nuclear bodies; IFN: Interferon.