Table 2.
Mechanisms of NSVs to counteract RLR signalling.
Interference with | Viral protein or function | Virus | Mechanism | References |
---|---|---|---|---|
RLR sensing | ssRNA encapsidation | all NSVs | Prevents dsRNA formation | [35], [36] |
dsRNA unwinding by cellular helicases UAP56 and URH49 | FLUAV, VSV | Prevents dsRNA formation | [50], [51] | |
Recruitment of La | ns-NSVs | Prevents RIG-I recognition of viral leader RNA | [39] | |
Regulation of RNA synthesis by viral proteins or promoter sequences | ns-NSVs, FLUAV | Prevents formation of aberrant RNAs | [45], [52], [53], [54], [55], [56], [57] | |
Nuclear replication | FLUAV | Hiding from cytoplasmic RLRs | [44] | |
VP35 | EBOV, MARV | dsRNA binding | [60], [61] | |
NS1 | FLUAV | dsRNA binding | [59], [62] | |
Cleavage of the 5′ppp RNA end to 5′p | Bornaviridae, Hantaviruses, CCHFV | Prevents RIG-I activation | [67], [68] | |
Genome RNA 5′overhang | Arenaviridae | Disturbs RIG-I function | [71] | |
dsRNA degradation by nucleocapsid protein | Lassa virus | Removes dsRNA | [72], [73] | |
RLR signalling | NS2 | RSV | Interacts with RIG-I to prevent association with MAVS | [75] |
Z | New World Arenaviruses | Interacts with RIG-I to prevent association with MAVS | [74] | |
OTU domain | Nairoviruses (Bunyaviridae) | De-ubiquitinylates RIG-I | [76], [77] | |
V | Paramyxoviruses | Wedges into MDA5 structure to prevent formation of signalling-competent filaments | [78], [79] | |
VP35 | EBOV | Sequesters the RIG-I cofactor PACT | [64] | |
V | Paramyxoviruses | Assemble RIG-I and LGP2 into a refractory complex | [80] | |
NS1 | FLUAV | Interacts with TRIM25 to counteract ubiquitinylation of RIG-I | [63] | |
Upregulation of Siglec-G by unknown mechanism | VSV, SeV (NSVs in general?) | Ubiquitin-mediated RIG-I degradation | [81] | |
NSs | TOSV | Ubiquitin-mediated RIG-I degradation | [82] | |
N and P | RSV | Recruitment of MDA5, MAVS, and RIG-I into inclusion bodies | [83] | |
NSs | SFTSV | Relocalization of RIG-I, TRIM25, TBK1, IKKɛ and IRF3 into inclusion bodies | [84], [85] | |
NS1 and NS2 | RSV | Formation of degradosome to destroy MAVS and IRFs | [86] | |
PB1, PB2, PA, PB1-F2 | FLUAV | Impairment of MAVS signalling | [87], [88], [89], [90], [91] | |
Nucleocapsid protein | Arenaviruses, hantaviruses | Prevention of TBK1 or IKKɛ activation | [93], [96] | |
Gn | Hantaviruses | Prevention of TBK1 action | [95] | |
P | BDV and Rabies | Prevention of TBK1 action | [92], [97] | |
V | Paramyxoviruses | Prevention of TBK1 activation | [94] | |
VP35 | EBOV | Prevents interactions of TBK1 and IKKɛ with IRFs | [66] | |
VP35 | EBOV | Inhibits IRF7 function by enhancing its SUMOylation via the cellular E3 ligase PIAS1 | [98] | |
ML | THOV | Blocks IRF3 and IRF7 dimerization and association with CBP, TRAF6 and the general transcription factor IIB | [99], [100] | |
V | Paramyxoviruses | Interact with IRF3 and impair nuclear translocation. | [101] | |
W | NiV | Inhibits activation of the IFN-β promoter | [102] | |
NSs | RVFV | Recruits repression factor SAP30 to inhibit IFN-β transcription | [103] | |
Host cell gene expression | Cap-snatching | s-NSVs | Destruction of host cell mRNAs by viral endonuclease function | [108] |
PA-X | FLUAV | Separate endonuclease domain, suppresses antiviral host cell responses | [109] | |
NS1 | FLUAV | Interferes with processing, nuclear export and translation of host mRNAs | [8] | |
M | VSV | Interferes with nuclear export of host mRNAs | [110] | |
NSs | RVFV | Disturbs assembly of TFIIH | [111] | |
NSs | RVFV | Promotes degradation of the TFIIH subunit p62 via the E3 ubiquitin ligase FBXO3. | [112], [113] | |
NSs | BUNV | Inhibits phosphorylation of the RNA polymerase II subunit RPB1 | [114] | |
NSs | LACV | Drives proteasomal degradation of RPB1 | [115] |