Table 4.

Virus‐encoded DUBs in host innate antiviral immunity.

Virus family	Virus	Virus‐encoded DUB	Host Target	Linkage	Rationale
RNA virus
Coronaviridae/ alphacoronaviruses	Human coronavirus NL63	PLP2	RIG‐I, TBK1, IRF3, STING	Lys48/63	Negatively regulate antiviral defenses by disrupting the STING‐mediated IFN induction[ 554 ]
	Mouse hepatitis virus	MHV PLP2	IRF3, TBK1	NA	Negatively regulate type I IFN signaling[ 555 , 556 ]
	Porcine epidemic diarrhea virus	PEDV PLP2	RIG‐I, STING	NA	Interfere with the RIG‐I‐ and STING‐mediated signaling[ 557 ]
Coronaviridae/ betacoronaviruses	SARS‐coronavirus (2)	SARS‐CoV PLpro	RIG‐I, TRAF3, STING, TBK1, IRF3, MDA5	Lys48/63, ISG15	Negatively regulate IRF3 activation.[ 558 , 559 ] Antagonize ISG15‐dependent activation of MDA5[ 560 ]
	MERS‐ coronavirus	MERS‐CoV PLpro	IRF3	Lys48/63, ISG15	Negatively regulate IRF3 activation[ 561 , 562 ]
Arteriviridae	Porcine reproductive and respiratory syndrome virus	PRRSV PLP2	RIG‐I	Lys6/11/27/29/33/48/63	Inhibits RIG‐I‐mediated IFN signaling[ 246 ]
			IκBα		Inhibit NF‐κB activation[ 563 ]
	Equine arteritis virus	EAV PLP2	RIG‐I	NA	Inhibits RIG‐I‐mediated IFN signaling[ 246 ]
Bunyaviridae/ nairoviruses	Crimean‐Congo hemorrhagic fever virus	CCHFV OTU	MDA5, RIG‐I	Lys6/11/48/63, ISG15	Inactivate RLR‐mediated innate immune signaling[ 246 ]
Arteriviridae	Simian hemorrhagic fever virus	SHFV PLP2	RIG‐I	NA	Inhibits RIG‐I‐mediated IFN signaling[ 246 ]
	Lactate dehydrogenase‐elevating virus	LDV PLP2	RIG‐I	NA	Inhibits RIG‐I‐mediated IFN signaling[ 246 ]
Picornaviridae	Dugbe virus	DUGV OTU	NA	Lys48/63	Negatively regulate type I IFN signaling[ 564 ]
	Foot‐and‐mouth disease virus	FMDV Lbpro	RIG‐I, TBK1, TRAF3, TRAF6	Lys48/63	Negatively regulate type I IFN signaling[ 565 ]
	Seneca valley viru	SVV 3Cpro	RIG‐I, TBK1, TRAF3	NA	block IFN‐β induction[ 252 ]
DNA virus
Adenoviridae	Adenovirus	Adenain	Histone H2A	Lys48, ISG15	Acquire an advantageous property by adenovirus[ 241 ]
Herpesviridae/ alphaherpesviruses	Herpes simplex virus	UL36USP	TRAF3	Lys48/63	Deubiquitinate TRAF3 and prevent the recruitment of the downstream adaptor TBK1[ 566 ]
			IκBα	Lys48	Restrict IκBα degradation and finally abrogate NF‐κB activation[ 567 ]
			STING	Lys48	Inhibits induction of type I IFN[ 253 ]
Herpesviridae/ betaherpesviruses	Human cytomegalovirus	pUL36USP	MLKL	Lys63	Degrade MLKL and inhibit necroptosis[ 568 ]
Herpesviridae/ gammaherpesviruses	Epstein‐Barr virus	BPLF1	PCNA	Lys48/63	Disrupt the cellular response to DNA damage[ 569 ]
			SQSTM1/p62		Regulate selective autophagy, which may promote infection and the production of infectious virus[ 570 ]
			Cullin		Benefit virus life cycle by inducing a replication‐permissive S‐phase‐like cellular environment[ 571 ]
			TRAF6		Deubiquitinate TRAF6 to inhibit NF‐κB signaling[ 572 ]
			TRAF6, NEMO, IκBα		Deubiquitinate signaling intermediates in the TLR cascade to counteract innate anti‐viral immunity[ 255 ]
	Kaposi's sarcoma‐associated herpesvirus	KSV ORF64	RIG‐I	Lys48/63	Suppresse RIG‐I‐mediated IFN signaling[ 573 ]
Herpesviridae	Hepatitis B virus	HBx	RIG‐I	Lys63	Evade the induction of IFN and IFN‐induced antiviral effects[ 574 ]
			RIG‐I, TBK1, CARDIF, TRIF, NEMO, IKKi, IRF3		Negatively regulate type I IFN production[ 575 ]