VAPA suppresses BEFV and VSV-induced type I IFNs signaling response by targeting JAK1 for NEDD4-mediated ubiquitin-proteasome degradation

IF 2.4 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology Pub Date : 2025-03-04 DOI:10.1016/j.vetmic.2025.110456

Tianhua Chen , Xingyu Li , Peili Hou, Hongbin He, Hongmei Wang

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引用次数: 0

Abstract

VAMP-associated protein A (VAPA) binds to various proteins involved in multiple cellular processes, however, its role in the regulation of type I interferons (IFN-I) signaling has not been elucidated. In this study, we demonstrate that VAPA negatively regulates the IFN-I signaling during bovine epidemic fever virus (BEFV) and vesicular stomatitis virus (VSV) infection. Upon treatment with IFN-β, VAPA negatively regulates the JAK-STAT signaling pathway. Further studies show that VAPA inhibits the IFN-I signaling by promoting the degradation of JAK1 through the ubiquitin-proteasome system during BEFV and VSV infection. Mechanistically, VAPA facilitates the interaction between the E3 ubiquitin ligase NEDD4 and JAK1, thereby enhancing the ubiquitination and subsequent degradation of JAK1. Furthermore, viral titers are markedly reduced, and the promoting effect of VAPA on VSV or BEFV replication is attenuated in NEDD4-deficient cells. Taken together, our findings reveal a novel role for VAPA in negatively regulating the IFN-I signaling response and provide a molecular basis for the design of targeted antiviral agents.

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来源期刊

Veterinary microbiology 农林科学-兽医学

CiteScore

5.90

自引率

6.10%

发文量

221

审稿时长

52 days

期刊介绍： Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal. Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge. Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.