Influenza D virus Matrix protein 1 restricts the type I interferon response by degrading TRAF6

Chen, Zhaoshan; Zeng, Yan; Wei, Yanli; Wang, Qian; Liu, Minxuan; Zhang, Bo; Liu, Junwen; Zhu, Qing; Xu, Shuai

doi:10.1016/j.virol.2022.01.001

Cited by 8 publications

(8 citation statements)

References 47 publications

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“…Previous studies have shown that TRAF6 contains an RF domain, a COIL domain, a ZnF domain, and a TRAF-C domain. [ 22 ] ASB3 is composed of two main functional structure domains, including the ANK domain and the SOCX domain. We found that ASB3 interacts only with the C-terminal structural domain of TRAF6 (Figure 5g).…”

Section: Resultsmentioning

confidence: 99%

ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota

Cheng,

Xu,

Sun

et al. 2023

Preprint

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BACKGROUND & AIMS: E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Our aim was to investigate the role of ASB3 in gut epithelium inflammation. METHODS: ASB3 was quantified in the lesions of IBD patients using Western blotting, qPCR and immunohistochemistry. We treated wild-type (WT) and ASB3-/- FVB-N mice and their derived colonic organoids with dextran sulfate sodium (DSS) or TNF-α as models of colitis and assessed inflammation onset, transcriptome, microbiome and ubiquitination modifications. RESULTS: ASB3-/- mice are resistant to DSS-induced colitis. IκBα phosphorylation levels and production of pro-inflammatory factors IL-1β, IL-6, and TNF-α were reduced in colonic tissues of ASB3-/- mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotic clearance of the microbiota. In addition, ASB3 specifically interacts with TRAF6 and degrades it via the proteasomal pathway. Further analysis revealed that ASB3 enhances K48-linked polyubiquitination of TRAF6 through the interaction of its SOCS box (SOCX) domain with the TRAF6 C-terminal domain. CONCLUSIONS: ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors production by disrupting the TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis.

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Section: Resultsmentioning

confidence: 99%

ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota

Cheng,

Xu,

Sun

et al. 2023

Preprint

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“…IDV matrix protein was shown to suppress RLR and NF-κB signaling in human cells HEK-293T by degrading the TNF receptor-associated factor 6 (TRAF6) ( 63 ), which is known to play a pivotal role in NF-κB activation ( 64 – 66 ) but also in the IFN-I pathway ( 67 ). Our RT-qPCR and ELISA results in bovine PCLSs indicate that a counteraction of the NF-κB pathway takes place also in cattle.…”

Section: Discussionmentioning

confidence: 99%

The Activation of the RIG-I/MDA5 Signaling Pathway upon Influenza D Virus Infection Impairs the Pulmonary Proinflammatory Response Triggered by Mycoplasma bovis Superinfection

Gaudino

Lion

Sagné

et al. 2023

J Virol

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“…Understanding host–pathogen interactions against IDV is critical for understanding why pathogenesis differs between IDV and other types of influenza virus. Protein components of the RNA-dependent RNA polymerase of both IAV and IBV, as well as the M1 protein of IAV, have all demonstrated antagonism of IFN response [ 4 , 11 , 42 , 43 , 44 , 45 , 46 ]. The IAV accessory proteins PB1-F2 and PA-X each stem from an alternate reading frame or single frameshift of the polymerase protein components of IAVs and have also been linked to anti-immune functions.…”

Section: Innate Immunity Against Influenzamentioning

confidence: 99%

“…As with other influenza virus types, the M1 protein of IDV is encoded on the matrix (M) gene. Recently, the M1 protein of IDV was found to negatively regulate type I IFN signaling using a similar mechanism to the M1 protein of IAV [ 46 ]. So far, the NS1 protein of IDV has only proved similar to its IAV and IBV analogs through its ability to interfere with innate immunity in vitro, while research suggests this immune response antagonism is lost in vivo [ 41 , 61 ].…”

Section: Innate Immunity Against Influenzamentioning

confidence: 99%

Comparing Influenza Virus Biology for Understanding Influenza D Virus

Skelton

Huber

2022

Viruses

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The newest type of influenza virus, influenza D virus (IDV), was isolated in 2011. IDV circulates in several animal species worldwide, causing mild respiratory illness in its natural hosts. Importantly, IDV does not cause clinical disease in humans and does not spread easily from person to person. Here, we review what is known about the host–pathogen interactions that may limit IDV illness. We focus on early immune interactions between the virus and infected host cells in our summary of what is known about IDV pathogenesis. This work establishes a foundation for future research into IDV infection and immunity in mammalian hosts.

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Influenza D virus Matrix protein 1 restricts the type I interferon response by degrading TRAF6

Cited by 8 publications

References 47 publications

ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota

ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota

The Activation of the RIG-I/MDA5 Signaling Pathway upon Influenza D Virus Infection Impairs the Pulmonary Proinflammatory Response Triggered by Mycoplasma bovis Superinfection

Comparing Influenza Virus Biology for Understanding Influenza D Virus

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