Suppression of NF-κB Activity: A Viral Immune Evasion Mechanism
Abstract
:1. Introduction
2. The Activation of the NF-κB
2.1. Receptors
2.2. Adaptor Proteins
2.3. IKKs, IκBα and p50/p65
3. Viruses Suppress NF-κB Activation
3.1. Targeting Receptors and Adaptor Proteins
3.2. Targeting IKKs
3.3. Targeting IκBα
3.4. Targeting p50/p65 and Reducing NF-κB Transcriptional Activity
4. The Specific NF-κB Inhibitors from Viruses
4.1. Proteases Encoded by Viruses
4.1.1. NS3/4A
4.1.2. The 3C and 3C-Like Proteases
4.2. DUBs Encoded by Viruses
4.2.1. Papain-Like Protease (PLP)
4.2.2. Other Viral DUBs
4.3. PDL Motifs Encoded by Viruses
4.4. PPase-Binding Proteins Encoded by Viruses
4.5. SH Protein Encoded by Viruses
5. Suppression of NF-κB Activity to Facilitate HIV-1 Immune Evasion
6. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Virus * | Viral Protein | Mechanisms of Modulation | Host Targets | References |
---|---|---|---|---|
HSV-1 | ICP0 | Promotes the degradation of MyD88 and TIRAP; binds to RHD of p50 and p65 | MyD88, TIRAP, p50, p65 | [26,62] |
Us3 | Reduces TRAF6 polyubiquitination and hyperphosphorylates p65 | TRAF6, p65 | [58,59] | |
UL24 | Binds to the RHD of p50 and p65 | p50, p65 | [60] | |
UL42 | Binds to the RHD of p50 and p65 | p50, p65 | [61] | |
VP16 | Binds to p65 and probably sequesters CBP | p65 | [72] | |
UL36 | Cleaves polyubiquitin chains from IκBα | IκBα | [96] | |
γ134.5 | Recruits both IKKα/β and PP1 to dephosphorylate IKKβ | IKKβ | [109] | |
VZV | ORF61 | Prevents β-TrCP-mediated IκBα ubiquitination | IκBα | [55] |
SVV | ORF61 | Binds to β-TrCP and interferes with IκBα ubiquitination | IκBα | [55] |
HCMV | pUL83 | Blocks IFI16 pyrin aggregation | IFI16 | [31] |
UL26 | Decreases phosphorylation of IKKα and IKKβ | IKKα, IKKβ | [49] | |
UL48 | Cleaves K48- and K63-linked polyubiquitin chains of RIP1 | RIP1 | [95] | |
MCMV | M45 | Disrupts DAI–RIP1 interactions or inhibits the ubiquitination of RIP1; induces degradation of NEMO | RIP1, NEMO | [32,33,34] |
KSHV | RTA | Reduces levels of expressed TLR2, TLR4 and MyD88; degrades MyD88 and TRIF | TLR2, TLR4, MyD88, TRIF | [21,24,25,30] |
LANA-1 | Causes p65 ubiquitination and degradation | p65 | [67] | |
ORF64 | Reduces the ubiquitination of RIG-I | RIG-I | [97] | |
EBV | BPLF1 | Removes ubiquitin chains from IκBα, TRAF6 and NEMO | IκBα, TRAF6, NEMO | [98] |
MuHV-4 | ORF73 | Causes p65 ubiquitination and degradation | p65 | [66] |
PV | 2C | Recruits both IKKα/β and PP1 to dephosphorylate IKKβ | IKKβ | [110] |
CVA16 | 2C | Recruits both IKKα/β and PP1 to dephosphorylate IKKβ | IKKβ | [110] |
CVB3 | 2C | Recruits both IKKα/β and PP1 to dephosphorylate IKKβ | IKKβ | [110] |
3C | Cleaves MAVS and TRIF | MAVS, TRIF | [80] | |
EV71 | 2C | Interacts with the IPI domain of p65; recruits both IKKα/β and PP1 to dephosphorylate IKKβ | p65, IKKβ | [63,110] |
3C | Cleaves TRIF, TAK1, TAB1, TAB2, and TAB3 | TRIF, TAK1, TAB1, TAB2, TAB3 | [82,87] | |
EV68 | 3C | Cleaves TRIF | TRIF | [81] |
FMDV | 3C | Cleaves NEMO | NEMO | [84] |
HAV | 3C | Cleaves NEMO | NEMO | [85] |
HBV | HBX | Promotes the degradation of MAVS | MAVS | [28] |
HBeAg | Interacts and colocalizes with Mal and TRAM; inhibits the expression of RIP2 | Mal, TRAM, RIP2 | [35,36,37] | |
HCV | NS3 | Decreases LUBAC-mediated linear ubiquitylation of NEMO | NEMO | [40] |
NS3/4A | Cleaves MAVS, TRIF, and Importin β1 | MAVS, TRIF, Importin β1 | [73,74,77,78,79] | |
HEV | ORF3 | Reduces the mRNA levels of TLR4, TLR6, NOD2, and TRADD | TLR4, TLR6, NOD2, TRADD | [22,23] |
HBoV | NS1-70 | Interacts with p65 RHD | p65 | [70] |
NS1 | Interacts with p65 RHD and inhibits the phosphorylation of p65 | p65 | [70] | |
JEV | NS5 | Blocks the interaction of importin α with p65 | importin α | [68] |
IAV | NS1 | Decreases phosphorylation of IKKα and IKKβ | IKKα, IKKβ | [53] |
CSFV | NS3 | Promotes the degradation of TRAF6 | TRAF6 | [27] |
RV | NSP1 | Binds to β-TrCP and interferes with IκBα degradation | IκBα | [100,101,102,103] |
PEDV | NSP1 | Inhibits the phosphorylation and degradation of IκBα | IκBα | [54] |
NSP5 | Cleaves NEMO | NEMO | [89] | |
PRRSV | NSP11 | Reduces the mRNA levels of both MAVS and RIG-I | MAVS, RIG-I | [20] |
NSP4 | Cleaves NEMO | NEMO | [88] | |
NSP2 | Interferes with the polyubiquitination of IκBα | IκBα | [93] | |
HTNV | N protein | Blocks the interaction of importin α with p65 | importin α | [69] |
CoV | ORF-9b | Promotes degradation of MAVS | MAVS | [29] |
SARS-CoV | PLP | Removes Lys63-linked ubiquitin chains of TRAF3 and TRAF6 | TRAF3, TRAF6 | [91] |
TGEV | PLP1 | Binds to and deubiquitinates RIG-I | RIG-I | [92] |
hMPV | M2-2 | Prevents MAVS from recruiting downstream molecules and interacts with MyD88 | MAVS, MyD88 | [38,39] |
SH | Unknown | Unknown | [118] | |
MuV | SH | Interacts with TNFR1, IL-1R1, and TLR3 complexes | TNFR1, RIP1, IRAK1 | [113,114] |
HIV-1 | Vpu | Binds to β-TrCP and diminishes degradation of IκBα, counteracts tetherin | IκBα, tetherin | [105,106,119,120] |
MCV | MC005 | Inhibits the activity of the conformational state of NEMO | NEMO | [41] |
MC159 | Interacts with NEMO | NEMO | [42] | |
MC160 | Reduces IKKα protein levels and the phosphorylation of IKKα and IKKβ | IKKα, IKKβ | [51,52] | |
MC132 | Causes p65 ubiquitination and degradation | p65 | [65] | |
VACV | C4 | Interacts with NEMO and IKKβ | NEMO, IKKβ | [43] |
B14 | Prevents IKKβ phosphorylation and activation | IKKβ | [45,46,47,48] | |
A49 | Binds to β-TrCP and diminishes degradation of IκBα | IκBα | [104] | |
ORFV | ORFV073 | Inhibits IKK activation, possibly by interacting with NEMO | Unknown | [44] |
ORFV024 | Decreases phosphorylation of IKKα and IKKβ | IKKα, IKKβ | [50] | |
ORFV121 | Binds to p65 and inhibits the phosphorylation of p65 | p65 | [64] | |
ORFV002 | Decreases acetylation of p65 | p65 | [71] | |
ECTV | EVM002 | Interacts with Skp1 via the F-box domain and diminishes the interaction between β-TrCP and the SCFβ-TrCP complex | Skp1 | [56,57] |
EVM005 | ||||
EVM154 | ||||
EVM165 | ||||
MCPyV | T antigen | Recruits a PP4R1/PP4C/PP2A Aβ phosphatase complex to dephosphorylate IKKs | NEMO | [111,112] |
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Deng, L.; Zeng, Q.; Wang, M.; Cheng, A.; Jia, R.; Chen, S.; Zhu, D.; Liu, M.; Yang, Q.; Wu, Y.; et al. Suppression of NF-κB Activity: A Viral Immune Evasion Mechanism. Viruses 2018, 10, 409. https://doi.org/10.3390/v10080409
Deng L, Zeng Q, Wang M, Cheng A, Jia R, Chen S, Zhu D, Liu M, Yang Q, Wu Y, et al. Suppression of NF-κB Activity: A Viral Immune Evasion Mechanism. Viruses. 2018; 10(8):409. https://doi.org/10.3390/v10080409
Chicago/Turabian StyleDeng, Liyao, Qiurui Zeng, Mingshu Wang, Anchun Cheng, Renyong Jia, Shun Chen, Dekang Zhu, Mafeng Liu, Qiao Yang, Ying Wu, and et al. 2018. "Suppression of NF-κB Activity: A Viral Immune Evasion Mechanism" Viruses 10, no. 8: 409. https://doi.org/10.3390/v10080409