Table. 1.

Module Targeted	Microbe	Protein	Mode of antagonization	Citation
Receptor
	Staphylococcus aureus	SSL3, SSL4	Bind TLR2 ectodomain	[63, 64]
SMOC
	African swine fever virus	ORF I329L	Possibly targets TRIF	[69]
	Coxsackievirus	3C	Degrades TRIF	[10]
	Enterovirus 68	3C	Cleaves TRIF	[70]
	Hepatitis C virus (HCV)	NS3-4A	Cleaves TRIF	[71]
	HCV	NS5A	Binds MyD88	[72]
	HSV-1	ICP0	Promotes degradation of Myd88 and TIRAP	[16]
	KSHV	RTA	Degrades TRIF	[73]
	Vaccinia virus (VACV)	A46R	Binds TIRAP, TRAM, MyD88, TRIF, TLR4	[13, 14]
	VACV	A52R	Binds IRAK2	[19]
	Brucella spp.	BtpB	Probable TIR domain containing	[74]
	Brucella melitensis	TcpB	Blocks TIR-TIR interactions and promotes degradation of MyD88 and TIRAP	[75]
	Escherichia coli	TcpC	Blocks TIR-TIR interactions	[75]
	S. aureus	TirS	Blocks TIR-TIR interactions	[12]
	Salmonella enterica serovar Enteritidis	TlpA	Blocks TIR-TIR interactions	[55]
	Yersinia pestis	YpTdp	Blocks TIR-TIR interactions	[11]
TRAF6/TAK1
	Herpes simplex virus (HSV-1)	Us3	Decreases levels of TRAF6 ployubiquitination	[21]
	Epstein-Barr virus (EBV)	BPLF1	Deubiquitinates TRAF6	[22, 23]
	Shigella flexneri	OspI	Deamidates UBC13	[24]
	Enteropathogenic E.coli (EPEC)	NleE	Modifies TAB2 and TAB3	[25]
	Yersinia spp.	YopJ	Acetylates TAK1	[26]
MAP kinases
	Ebola virus	VP24	Blocks phosphorylation of p38	[28]
	Hepatitis B virus	HBsAg	Inhibits phosphorylation of JNK1/2 and c-Jun	[29]
	Bacillus anthracis	LF	Degrades MAPKK 1 and 2	[76]
	EPEC	NleC and NleD	Cleaves JNK	[50]
	Salmonella typhimurium	AvrA	Acetylates MKK4	[77]
	Salmonella spp.	SpvC	Modifies c-Jun, Erk1/2, and p38	[56, 57]
	S. flexneri	OspF	Modifies c-Jun, Erk1/2, and p38	[56, 78]
	Vibrio parahemolyticus	VopA	Acetylates MAPKK	[79]
	Yersinia spp.	YopJ	Acetylates MKK6, MKK4, MKK7	[26, 58]
NEMO complex
	EBV	BPLF1	Deubiquitinates NEMO	[23]
	Foot-and-mouth disease virus	3C	Cleaves NEMO	[31]
	Hepatitis A virus	3C	Cleaves NEMO	[32]
	HCV	NS3	Binds TBK1	[80]
	HSV-1	γ34.5	Binds TBK1	[81]
	Mouse hepatitis virus A59	NSp3 (PLP2 domain)	Deubiquitinates TBK1	[82]
	Sendai virus	C-protein	Binds IKKα	[33]
	VACV	B14R	Binds IKKβ	[83]
	VACV	C6	Binds TANK, SINTBAD, or NAP1	[84]
	VACV	N1L	Associates with IKK complex and TBK1	[54]
	VACV	K7R	Binds DDX3	[85]
	S. flexneri	IpaH9.8	Promotes NEMO degradation	[86]
	Yersinia spp.	YopJ/P	Acetylates IKKβ	[87]
Transcription factors
	Classical Swine Fever Virus	Npro	Interacts with IRF7	[88]
	EBV	BPLF1	Deubiquitinates IκBα	[23]
	HIV	Vpr, Vif	Degrade IRF3	[89, 90]
	HIV	Vpu	Possibly blocks IRF3 and NF-κB	[90, 91]
	HSV-1	ICP27	Stabilizes IkBa	[36]
	HSV-1	ICP0	Sequesters IRF3- CBP/p300	[42]
	HSV-1	Us3	Phosphorylates IRF3 and NF-kB	[40, 41]
	HSV-1	VP16	Binds CBP in the nucleus	[44]
	KSHV	RTA	Promotes degradation of IRF3 and IRF7	[92]
	KSHV	K-bZIP	Competes for IRF3 binding sites	[93]
	KSHV	vIRF-1	Inhibits IRF3 interaction with CBP and p300	[43]
	KSHV	vIRF3	Binds IRF3	[94]
	Measles virus	C-protein	Unknown function in nucleus	[95]
	Measles virus	V-protein	Binds NF-kB and IRF3	[96]
	Mumps virus	V-protein	Mimics IR3	[97]
	Rotavirus	NSP1	Degrades IRF3, IRF7 or E3 ligase β-TrCP	[37, 98, 99]
	Sendai virus and New castle disease virus	V-protein	Binds active IRF3 and prevents nuclear translocation	[96]
	VACV	A49	Binds and inhibits β-TrCP	[38]
	Varicella-Zoster virus (VZV)	ORF47	Atypically phosphorylates IRF3	[39]
	VZV	ORF61	Ubiquitinates IRF3 and NF-kB	[100, 101]
	EPEC	NleC,NleD	Cleaves NF-κB	[47–50]
	EPEC	NleB, NleE	Inhibits nuclear translocation of NF-kB	[51]
	EPEC and enterohemorrhagic Escherichia coli (EHEC)	NleH1, NleH2	Inhibits nuclear translocation of NF-kB	[45, 46]
	S. flexneri	OspZ	Inhibits nuclear translocation of NF-kB	[51]
	S. flexneri	OspG	Binds and interferes with UbcH5b	[52]