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Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

Liu Y, Zhu Z, Zhang M, Zheng H - Vet. Res. (2015)

Bottom Line: In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects.To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules.In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China. 496104087@qq.com.

ABSTRACT
Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

No MeSH data available.


Related in: MedlinePlus

DUB activity of Lproin innate immune signaling pathways. Lpro can deubiquitinate several adaptor proteins including RIG-I, TRAF3, TRAF6, and TBK1. Deubiquitination of these proteins contributes to the attenuation of host innate immune responses.
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Fig3: DUB activity of Lproin innate immune signaling pathways. Lpro can deubiquitinate several adaptor proteins including RIG-I, TRAF3, TRAF6, and TBK1. Deubiquitination of these proteins contributes to the attenuation of host innate immune responses.

Mentions: A recent study from Wang et al. has identified a DUB-like activity of Lb of FMDV [22]. It was observed that Lb significantly inhibited ubiquitination of several adaptor signaling molecules of type I IFN pathway, including RIG-I, TBK1, TRAF3, and TRAF6 (Figure 3). The results of sequence alignment and structural bioinformatics analyses indicate that Lpro and ubiquitin-specific protease (USP)14 share similar topology [91]. The DUB activity of Lb was further confirmed through observation of the inhibitory effects of Lb on ubiquitination of RIG-I, TRAF3, TRAF6, and TBK1, which eventually prevents activation of the type I IFN pathway. This DUB activity can be abrogated through mutation of the conserved catalytic sites of Lb. The deubiquitinating processes mediated by Lb are similar to those mediated by DUBA and CYLD. Future studies should focus on whether the DUB activity of Lb is involved in the signaling pathways regulated by A20.Figure 3


Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

Liu Y, Zhu Z, Zhang M, Zheng H - Vet. Res. (2015)

DUB activity of Lproin innate immune signaling pathways. Lpro can deubiquitinate several adaptor proteins including RIG-I, TRAF3, TRAF6, and TBK1. Deubiquitination of these proteins contributes to the attenuation of host innate immune responses.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4625562&req=5

Fig3: DUB activity of Lproin innate immune signaling pathways. Lpro can deubiquitinate several adaptor proteins including RIG-I, TRAF3, TRAF6, and TBK1. Deubiquitination of these proteins contributes to the attenuation of host innate immune responses.
Mentions: A recent study from Wang et al. has identified a DUB-like activity of Lb of FMDV [22]. It was observed that Lb significantly inhibited ubiquitination of several adaptor signaling molecules of type I IFN pathway, including RIG-I, TBK1, TRAF3, and TRAF6 (Figure 3). The results of sequence alignment and structural bioinformatics analyses indicate that Lpro and ubiquitin-specific protease (USP)14 share similar topology [91]. The DUB activity of Lb was further confirmed through observation of the inhibitory effects of Lb on ubiquitination of RIG-I, TRAF3, TRAF6, and TBK1, which eventually prevents activation of the type I IFN pathway. This DUB activity can be abrogated through mutation of the conserved catalytic sites of Lb. The deubiquitinating processes mediated by Lb are similar to those mediated by DUBA and CYLD. Future studies should focus on whether the DUB activity of Lb is involved in the signaling pathways regulated by A20.Figure 3

Bottom Line: In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects.To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules.In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, OIE/National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China. 496104087@qq.com.

ABSTRACT
Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

No MeSH data available.


Related in: MedlinePlus