Table 1.

Examples of RNA viral antagonism upstream of IFN induction

Viral family	Virus	Proposed mechanism of evasion upstream of IFN signalling	References
Flaviviridae	DENV, WNV, ZIKV and JEV	Viral protease NS2B3 cleaves STING	14, 91,118
Flaviviridae	YFV	Viral protein NS4B interacts with STING	124
Flaviviridae	HCV	Viral protein NS4B interacts with and disrupts STING signalling complexes	125,126
Coronaviridae	HCoV-NL63	Viral protein PLP2–TM interacts with and disrupts STING signalling complexes	127,128
Coronaviridae	PEDV	Viral protein PLP2 interacts with and disrupts polyubiquitination of STING	129
Coronaviridae	SARS-CoV	Viral protein Plpro–TM interacts with and disrupts STING signalling complexes	127, 128,130
Flaviviridae	HCV	Viral protease NS34A cleaves MAVS	131,132
Picornaviridae	HAV	Viral protease precursor 3ABC cleaves MAVS	133
Flaviviridae	DENV	Viral protease NS2B3 cleaves MAVS	134
Flaviviridae	HCV	Viral protease NS34A cleaves TRIF	135
Picornaviridae	HAV	Viral protease intermediate cleaves TRIF	136
Arteriviridae and Bunyaviridae	Arterivirus and nairovirus	Viral protease deubiquinates RIG-I	137
Arenaviridae	Arena virus synthetic molecules	Viral 5’ppp overhangs act as RIG-I decoy	138
Arenaviridae	GTOV, JUNV, MAVC and SABV	Viral Z protein binds to and inhibits RIG-I	139
Paramyxoviridae	hPIV5	Viral V protein binds LGP2, cooperatively inhibiting induction by RIG-I ligands	140
Reoviridae	Synthetic reovirus RNA mimics	Synthetic particles trigger RIG-I; virus trims 5’ppp for innate immune evasion	141
Orthomyxoviridae	IAV	Viral protein NS1 binds RIG-I and prevents activation; RIG-I selectively evolved to distinguish self from non-self	142,143
Bornaviridae	BDV	Viral P protein antagonizes TBK1	144
Bunyaviridae	SFTSV	Viral protein NSs sequesters TBK1/IKK-ε	145
Bunyaviridae	Hantavirus	Dephosphorylation of TBK1/IRF3	146–148
Filoviridae	Ebola virus	Viral protein VP35 sequesters viral RNA	149,150
Togaviridae	Sindbis virus	Viral protein nsP2 downregulates IFN and minimizes virus visibility	151
Bunyaviridae	ANDV	Viral NP and GPC proteins inhibit IFN-β induction	152
Bunyaviridae	SNV	Viral GPC protein inhibits IFN-β induction	152
Bornaviridae	BDV	Evades detection by genome trimming	153

GTOV, Guanarito virus; JUNV, Junin virus; MAVC, Machupo virus; SABV, Sabia virus; PLP2, papain-like protease 2; TM, transmembrane domain; VP35, virion protein 35; SFTSV, severe fever with thrombocytopenia syndrome virus; GPC, glycoprotein precursor; PEDV, porcine epidemic diarrhea virus; Plpro, papain-like protease; 3ABC, stable intermediate product of HAV polyprotein processing including viral proteins 3A, 3B and 3C; nsP2, non-structural protein 2; NP, nucleocapsid protein.