2020
DOI: 10.1128/jvi.01850-19
|View full text |Cite
|
Sign up to set email alerts
|

Binding of Duck Tembusu Virus Nonstructural Protein 2A to Duck STING Disrupts Induction of Its Signal Transduction Cascade To Inhibit Beta Interferon Induction

Abstract: Duck Tembusu virus (DTMUV), which is similar to other mosquito-borne flaviviruses that replicate well in most mammalian cells, is an emerging pathogenic flavivirus that has caused epidemics in egg-laying and breeding waterfowl. Immune organ defects and neurological dysfunction are the main clinical symptoms of DTMUV infection. Preinfection with DTMUV makes the virus impervious to later interferon (IFN) treatment, revealing that DTMUV has evolved some strategies to defend against host IFN-dependent antiviral re… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

2
40
0

Year Published

2020
2020
2024
2024

Publication Types

Select...
8

Relationship

1
7

Authors

Journals

citations
Cited by 36 publications
(42 citation statements)
references
References 48 publications
2
40
0
Order By: Relevance
“…Furthermore, they found that DTMUV NS2B3 cleaves duck STING (duSTING) through an NS2B dependent manner and that the binding of NS2B with duSTING distal tail (residue 221-225) is a prerequisite for the subsequent cleaving by NS2B3 complex. Moreover, in their latest work, they discovered that DTMUV NS2A competes with duck TBK1 (duTBK1) to bind with duSTING, thus disrupting duSTING dimerization and inhibiting downstream IFN production [88]. The work they performed using an avian model will undoubtedly inform the work we do in mammalian systems in the future and could potentially provide evidence for a conserved pan-flavivirus strategy of modulating host innate immune space by targeting the cGAS/STING pathway [138,139].…”
Section: Duck Tembusu Virusmentioning
confidence: 96%
See 1 more Smart Citation
“…Furthermore, they found that DTMUV NS2B3 cleaves duck STING (duSTING) through an NS2B dependent manner and that the binding of NS2B with duSTING distal tail (residue 221-225) is a prerequisite for the subsequent cleaving by NS2B3 complex. Moreover, in their latest work, they discovered that DTMUV NS2A competes with duck TBK1 (duTBK1) to bind with duSTING, thus disrupting duSTING dimerization and inhibiting downstream IFN production [88]. The work they performed using an avian model will undoubtedly inform the work we do in mammalian systems in the future and could potentially provide evidence for a conserved pan-flavivirus strategy of modulating host innate immune space by targeting the cGAS/STING pathway [138,139].…”
Section: Duck Tembusu Virusmentioning
confidence: 96%
“…Although the focus of this review is on the mammalian cytosolic DNA sensory system and the flaviviral strategies on regulation and modulation of those pathways, the authors believe it is noteworthy to mention some elucidating new research coming from the field of avian flavivirus (duck Tembusu virus, or DTMUV) [88,89,137].…”
Section: Duck Tembusu Virusmentioning
confidence: 99%
“…The NS2A protein and TBK1 competed binding to duck STING, disrupted STING dimer formation and reduced TBK1 phosphorylation, leading to the inhibition of IFN-β production. The amino acid residues at 164, 167, and 361 in STING were important for NS2A binding with STING [145]. However, NS2B3 polyproteins inhibited IFN induction by hydrolyzing duck STING, and further mapping analysis showed the scissile bond located between the R84 and G85 residues of STING [146].…”
Section: Inhibition Of Ifn Production By Targeting Important Adaptor mentioning
confidence: 97%
“…Additionally, in our previous study, we analyzed the ability of the 10 proteins encoded by duck TMUV to block the IFN system and found that the expression of NS2A, NS2B, and 2KNS4B resulted in robust IFN signaling inhibition. We further found that duck TMUV NS2A inhibited IFNb induction by targeting duck STING (13), and duck TMUV NS2B3 could cleave and bind duck STING to subvert the induction of IFNb (14), suggesting that different duck TMUV proteins could commonly target the same cellular components through different strategies to suppress IFNb production. However, the mechanism by which duck TMUV NS4B subverts the host innate immune response is unclear and requires further study.…”
Section: Introductionmentioning
confidence: 77%
“…The sequence of the 2KNS4B gene was amplified from the duck TMUV CQW1 strain genome and cloned into the pCAGGS expression vector with a His tag at the C terminus using standard molecular biology techniques. The plasmids pCAGGS-duRIG-I, duMDA5, duMAVS, duTBK1, duIRF7, and duSTING-Flag and pBiT-LgBiT-duRIG-I, duMDA5, duMAVS, duTBK1, duIRF7, duSTING-Myc, pBiT-SmBiT-duTBK1 and STING-Flag were constructed as described in our previous study (13) for the NanoLuc Binary Technology (NanoBiT) assay. 2KNS4B and its truncations or mutants were cloned into pBiT2.1C-SmBiT with a Flag tag.…”
Section: Plasmid Constructsmentioning
confidence: 99%