Veterinary Research最新文献

{"title":"African swine fever virus MGF505-4R facilitates cGAS degradation through TOLLIP-mediated selective autophagy and inhibits the formation of ISGF3 to evade innate immunity.","authors":"Manman Yao, Pengfei Li, Xiangmin Li, Wentao Li, Ping Qian","doi":"10.1186/s13567-025-01569-x","DOIUrl":"10.1186/s13567-025-01569-x","url":null,"abstract":"<p><p>African swine fever virus (ASFV) causes acute and highly lethal disease in pigs. To counteract host defense systems and facilitate virus infection, many ASFV-encoded proteins have regulatory effects on the innate immune response. In this study, we constructed an MGF505-4R-deleted ASFV strain (ASFV-Δ4R) and found that, compared with the wild-type ASFV, ASFV-Δ4R infection significantly increased IFN-β production and elevated the mRNA levels of antiviral genes in porcine alveolar macrophages. Mechanistically, MGF505-4R interacts with cGAS and promotes its degradation by triggering Toll-interacting protein (TOLLIP)-mediated selective autophagy. Specifically, MGF505-4R enhanced the interaction between cGAS and TOLLIP, which subsequently led to increased degradation of cGAS. Additionally, MGF505-4R inhibited IFN-β-induced signal transmission by interacting with STAT1 and STAT2 and impeding their phosphorylation. This effect consequently prevented the formation of the ISGF3 heterotrimer and its subsequent translocation to the nucleus, leading to the downregulation of antiviral genes. As expected, compared with the ASFV-WT strain, ASFV-Δ4R infection increased phosphorylation of STAT1 and STAT2 and subsequent ISGF3 formation, leading to an elevated expression of antiviral gene ISGs. This discovery enhances the understanding of the immune regulation strategies evolved by ASFV and offers valuable perspectives for antiviral research targeting ASFV.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"137"},"PeriodicalIF":3.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel pilus-associated gene cluster is implicated in Streptococcus agalactiae virulence.","authors":"Wanyou Xu, Qiangsheng Lu, Meijuan Tian, Lvfeng Yuan, Yangming Song, Qiaoying Zeng, Jie Peng","doi":"10.1186/s13567-025-01567-z","DOIUrl":"10.1186/s13567-025-01567-z","url":null,"abstract":"<p><p>Streptococcus agalactiae (S. agalactiae), also known as Group B Streptococcus (GBS), is an important zoonotic pathogen. It is an important pathogen that causes bovine mastitis and can also lead to severe infections in newborns, pregnant women, and individuals with a weakened immune system. Adhesion to host cells is the first critical step in S. agalactiae infection, making the identification of key adhesion-related genes essential for understanding the pathogenic mechanisms of GBS. In this study, we used the Tn transposon system to construct a mutant library of S. agalactiae A909 and employed the mouse mammary epithelial cell line EPH4-Ev as a model to screen and validate adhesion-related genes. Our results revealed a gene cluster containing BP, AP1, and SrtC. While these genes did not affect the basic biological characteristics of the bacteria, they significantly influenced the adhesion rate to cells and the virulence of A909 in mice. Further transcriptomic analysis revealed that the Tnfsf15 gene plays a critical role in the regulation of A909 strain pathogenicity mediated by the BP, AP1, and SrtC gene clusters during host infection.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"135"},"PeriodicalIF":3.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porcine reproductive and respiratory syndrome virus NSP5 exploited UBE2L6 to promote viral replication via antagonising host RLRs and ISGylation.","authors":"Zhenbang Zhu, Lulu Chen, Meng Zhang, Qianwen Lin, Yifan Yan, Wenqiang Wang, Wei Wen, Zhendong Zhang, Xiangdong Li","doi":"10.1186/s13567-025-01558-0","DOIUrl":"10.1186/s13567-025-01558-0","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits the host innate immune response to promote its replication. The ubiquitin-proteasome system (UPS) and ISGylation both play roles in modulating host innate immunity. Within this process, ISG15-conjugating enzyme E2L6 (UBE2L6) functions as an E2 ubiquitin/ISG15-conjugating enzyme, which is crucial for the enzymatic cascades of UPS and ISGylation. However, the role of UBE2L6 during PRRSV infection remains unclear. Here, we report that UBE2L6 was up-regulated at both the transcript and protein levels during PRRSV infection. Overexpression of UBE2L6 facilitated PRRSV replication, whereas knockdown of UBE2L6 reduced viral replication. Mechanistically, UBE2L6 promoted the degradation of RIG-I and MDA5 protein expression via the ubiquitin-proteasome pathway and decreased ISGylation levels during PRRSV infection, thereby inhibiting the expression of type I interferons and interferon-stimulated genes (ISGs). In addition, UBE2L6 interacted with PRRSV NSP5 and stabilised the NSP5 protein. Together, PRRSV NSP5 and UBE2L6 further facilitated the degradation of RIG-I and MDA5 via the K48-linked ubiquitination pathway, ultimately facilitating PRRSV replication. Notably, UBE2L6 had minimal impact on RIG-I and MDA5 expression in the absence of PRRSV infection. In summary, UBE2L6 regulated host innate immunity and viral replication through its ubiquitination and ubiquitination-like functions. These findings provide novel insights into how PRRSV NSP5 exploits the host UPS to inhibit the innate immune response and deepen our understanding of the mechanism of host-virus interaction.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"136"},"PeriodicalIF":3.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escherichia coli is implicated in the development and manifestation of host susceptibility to the roundworm Trichostrongylus colubriformis infections in sheep.","authors":"Fang Liu, Jody McNally, Damarius Flemming, Aaron B Ingham, Peter William Hunt, Robert W Li","doi":"10.1186/s13567-025-01565-1","DOIUrl":"10.1186/s13567-025-01565-1","url":null,"abstract":"<p><p>Applied breeding for host resistance to gastrointestinal nematodes represents a cost-effective strategy for parasitic control. While resistance is under moderate genetic influences, gut microbial components involved in the development of resistance or susceptibility remain largely unknown. Here we characterize the structure and metabolic potential of the proximal colon microbiota in unique ovine populations bred for resistance and susceptibility using a full-length 16S rRNA gene sequencing-based microbiome approach. The resistant lambs produced significantly fewer parasite eggs than susceptible animals grazing on the same pasture. Further, the resistant lambs displayed a significant reduction in worm establishment in response to a Trichostrongylus colubriformis challenge infection (P < 0.0001; N = 20 per group). Among 32 bacterial species or strains displaying a significant difference in relative abundance between the resistant and susceptible group, E. coli was more abundant in susceptible lambs. E. coli was also ranked as the most important species in distinguishing the resistant and susceptible status. Moreover, a microbial signature or balance consisting of E. coli (Numerator) and Parabacteroides distasonis and Bacteroides thetaiotaomicron (Denominator) predicted the resistance status with high accuracy. The metagenome function prediction also revealed that several pathways related to infectious diseases, such as Shigellosis and pathogenic E. coli infection, were significantly altered between the two phenotypes. Our findings demonstrated that microbial signatures with a high predictive power for the resistance status can be developed as biomarkers to facilitate the selection for host resistance in sheep.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"133"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bacteriophage-based virus-like particle vaccine induces cross-reactive neutralising antibodies against porcine epidemic diarrhoea viruses (PEDV).","authors":"Jixiang Gu, Xu Zheng, Chunhui Li, Shipeng Wang, Xiangyu Xie, Martin F Bachmann, Yuchen Nan, Liang Li, Pei Sun, Lisha Zha, Xinyue Chang","doi":"10.1186/s13567-025-01559-z","DOIUrl":"10.1186/s13567-025-01559-z","url":null,"abstract":"<p><p>Although vaccines against porcine epidemic diarrhoea viruses (PEDV) are available, PED outbreaks continue to occur in many countries due to the emergence of new variants. Therefore, further endeavours are necessary to develop efficient and broadly protective vaccines. In this context, we present a nanoparticle vaccine candidate, referred to as AP205-S1, which successfully elicited antibody responses in mice and pigs. The vaccine was created by coupling the S1 protein of PEDV-KB2013, a G-II strain, to a bacterially expressed AP205-VLP using the SpyCatcher/SpyTag system. The AP205-S1 vaccine demonstrated an intact and homogenous viral particle structure, incorporating E. coli-derived ssRNA. Upon administration in mice, AP205-S1 induced high levels of S1-specific IgG antibodies in both serum and the gastrointestinal tract, particularly following a booster dose. Importantly, these antibodies were capable of neutralising PEDV in vitro, suggesting that the vaccine can generate protective antibodies against PEDV infection. Notably, the antibodies elicited by AP205-S1 exhibited cross-neutralising potential against a G-I strain, PEDV-AH2018-HF1, which was preserved in our lab. Additionally, S1-specific IgG antibodies were stimulated in piglets following immunisation with AP205-S1, and these antibodies could neutralise PEDV in vitro. Interestingly, piglets immunised with AP205-S1 exhibited lower viral loads compared to control piglets following a viral challenge. In conclusion, we developed a VLP-based vaccine candidate against PEDV, which demonstrated excellent immunogenicity in both mice and piglets, potentially providing protection against viral infection. Our work offers an effective option for preventing future PEDV epidemics.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"128"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated microRNAs in blood correlate with central nervous system neuropathology of prion disease.","authors":"Sonia Pérez-Lázaro, Inmaculada Martín-Burriel, Luca Cozzuto, Julia Ponomarenko, Juan J Badiola, Rosa Bolea, Janne M Toivonen","doi":"10.1186/s13567-025-01566-0","DOIUrl":"10.1186/s13567-025-01566-0","url":null,"abstract":"<p><p>The role of microRNAs (miRNAs) in neurodegenerative diseases has gained significant attention because of their involvement in gene regulation and potential as biomarkers. In prion diseases, including scrapie, miRNAs may modulate pathogenesis and disease progression. This study investigated circulating miRNA profiles in the blood of sheep naturally affected by scrapie at preclinical and clinical stages using small RNA sequencing and RT-qPCR validation. While only one novel miRNA was dysregulated in preclinical blood samples, 66 previously annotated miRNAs were significantly dysregulated in clinical sheep compared with healthy sheep. These miRNAs are associated with pathways commonly altered in neurodegenerative diseases, such as autophagy, ubiquitin-mediated proteolysis, and endoplasmic reticulum protein processing. Notably, miR-1271-5p, let-7f-5p, miR-186-5p, and miR-425-5p were consistently upregulated in the central nervous system of clinical animals, replicating the results observed in blood, with an increasing trend already in the preclinical stage and a strong correlation with neuropathological prion features. Additionally, predicted target genes such as UBQLN2, PGK1, KRAS, and CLTC were inversely expressed relative to these miRNAs, supporting their regulatory roles. These findings highlight the relevance of circulating miRNAs in prion neuropathology and support further research into the specific functional roles of these miRNAs and their predictive capacity for disease progression.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"132"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CRM1-dependent NES^257-266 motif in the matrix protein: another factor influencing Newcastle disease virus propagation and virulence.","authors":"Yaodong Zhang, Jun Dai, Lei Tan, Daoe Mu, Ziyan Zhang, Cuiping Song, Yang Qu, Ning Tang, Ying Liao, Chan Ding, Yingjie Sun, Xusheng Qiu","doi":"10.1186/s13567-025-01552-6","DOIUrl":"10.1186/s13567-025-01552-6","url":null,"abstract":"<p><p>As an important structural protein of Newcastle disease virus (NDV), the M protein plays a crucial role in the assembly and budding of the virus. In previous reports, we confirmed the existence of a classical nuclear export signal (NES) sequence on the M protein (i.e., amino acids 257 to 266), which plays an important role in the nuclear export of the protein. In this study, we found that the NES^257-266 motif is associated with the evolutionary history of NDV, and found that the NES-mediated nuclear export efficiency of M proteins varies among different genotypes. Further research on the LaSota-NES and JSD0812-NES variants showed that the NES both affects the nuclear-cytoplasmic trafficking efficiency of M protein and influences the formation of virus-like particles (VLPs). The NES^257-266 conforms to the chromosome region maintenance 1 (CRM1)-associated consensus leucine/isoleucine-rich NES motif, and our results confirm that the NES-mediated nuclear-cytoplasmic trafficking of M protein is dependent on the CRM1 pathway. At last, several recombinant LaSota strains were rescued using reverse genetics, with their NES sequence replaced by either a potent NES motif, or an R247K mutation, or both. The rescued rLaSota-QMS and rLaSota-FM strains showed elevated hemagglutination (HA) titers, increased 50% egg infective dose (EID₅₀) values, along with marginally higher mean death time (MDT) and intracerebral pathogenicity index (ICPI) values, all of which are attributable to their enhanced proliferation rates when compared to the wild-type (wt) rLaSota strain. Our findings contribute to a better understanding of the molecular mechanisms of replication and pathogenicity in NDV and, by extension, in other paramyxoviruses.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"126"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early dynamics of Toxoplasma gondii infection in sheep inoculated at mid-gestation with archetypal type II oocysts.","authors":"Roberto Sánchez-Sánchez, Pilar Horcajo, Miguel Fernández, David Arranz-Solís, Natalia Velasco-Jiménez, Michela Re, Daniel Gutiérrez-Expósito, Guillermo Valdivia, Angela Alonso-Diez, Julio Benavides, Luis Miguel Ortega-Mora","doi":"10.1186/s13567-025-01557-1","DOIUrl":"10.1186/s13567-025-01557-1","url":null,"abstract":"<p><p>Early abortion is a clinical presentation of ovine toxoplasmosis that occurs in the second week post-infection (pi), which is characterised by placental infarcts, foetal leukomalacia and absence of parasites in the placenta and foetal tissues. The pathogenic mechanism of early abortion is unknown, and descriptions of the early dynamics of T. gondii infection in pregnant sheep are scarce. The aim of this study was to investigate the presence of lesions and parasite DNA in the small intestine, mesenteric lymph nodes and placenta/foetus, that could be key during the first week after oral infection in sheep at mid-pregnancy. In the small intestine, lesions were rare and parasite DNA detection rates were low (3-8%), with the highest parasite DNA detection and burden found on day 6 pi in the Peyer's patches of the medial jejunum. In the mesenteric lymph nodes, adenomegaly and microscopic lesions were mainly observed on day 6 pi. Parasite DNA was detected in 11% and 61.2% of the samples from mesenteric lymph nodes on days 3 and 6 pi, respectively, with higher parasite DNA detection rates and burdens in the medial and distal jejunal lymph nodes on day 6 pi. In the placentomes, on day 6 pi, gross lesions were not observed, although significant histological changes, such as endothelial activation and vascular thrombosis, were found in 18.6% and 8.3% of the placentomes, respectively. These findings lay the groundwork for future research aimed at elucidating the precise mechanisms underlying early abortions following T. gondii infection in pregnant sheep.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"134"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outer membrane vesicles of Glaesserlla parasuis activate the endosomal cGAS-STING-IRF3 pathway through nucleic acid payload delivery: a biological perspective on host defense protocol optimization.","authors":"Kunli Zhang, Zeyi Sun, Xintong Kang, Keda Shi, Pinpin Chu, Dongxia Yang, Zhibiao Bian, Yan Li, Hongchao Gou, Zhiyong Jiang, Nanling Yang, Xia Zhou, Sutian Wang, Zhanyong Wei, Shaolun Zhai, Huahua Kang, Chunling Li","doi":"10.1186/s13567-025-01553-5","DOIUrl":"10.1186/s13567-025-01553-5","url":null,"abstract":"<p><p>Glaesserlla parasuis (G. parasuis), a Gram-negative pathogen responsible for Glässer's disease, employs outer membrane vesicles (OMVs) as sophisticated nanoscale effectors to modulate host‒pathogen interplay. While bacterial OMVs are recognized as critical mediators of virulence dissemination, their functional orchestration in G. parasuis immunopathogenesis remains unclear. To date, few reports have focused on the relationships among G. parasuis, OMVs and host-susceptible cells; thus, more evidence is urgently needed to explore their crosstalk further. This study revealed a novel immune activation paradigm: both G. parasuis and its OMVs trigger robust type I interferon (IFN) responses via a DNA-sensing cascade. G. parasuis OMVs-Dio were internalized by macrophages in a time-dependent manner, partially via clathrin-mediated endocytosis but mainly via dynamin-dependent endocytosis. Studies have shown that IFNs play key antiviral roles in viral infections and important roles in bacterial infections. Our results suggested that IFNs inhibited G. parasuis adhesion and invasion of pulmonary alveolar macrophage (PAM) cells. Furthermore, by assessing the major components of OMVs, we confirmed that the DNA of G. parasuis, which is carried by OMVs, is the key component that induces the production of IFN in macrophages. The cGAS-STING-IRF3 pathway links the host's recognition of G. parasuis OMVs to IFN production. Taken together, our data reveal that G. parasuis OMVs activate cGAS/STING/IRF3 signaling and induce IFN production, which then affects the adhesion and invasion of G. parasuis. The discovery of this vesicle-mediated nucleic acid delivery system redefines the pathogenesis framework for G. parasuis and provides a trans-species conceptual advance in understanding how Gram-negative pathogens exploit vesicular trafficking to manipulate host immunity.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"127"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host cellular protein RAB33B facilitates influenza viral replication and modulates M2 trafficking by enhancing autophagy.","authors":"Shaotang Ye, Zhen Wang, Gang Lu, Aolei Chen, Liang Xu, Yongbo Liu, Jianwei Mao, Jingyu Wang, Gaoming Lou, Qingmei Xie, Kun Jia, Shoujun Li","doi":"10.1186/s13567-025-01560-6","DOIUrl":"10.1186/s13567-025-01560-6","url":null,"abstract":"<p><p>Influenza A virus (IAV) remains a major global health threat. Its M2 protein plays crucial roles in viral fusion, transportation, assembly, and release. Recent studies have shown that IAV impairs host autophagy flux to enhance viral replication. However, the precise mechanisms by which IAV M2 manipulates host cellular autophagy during virus replication remain unclear. In this study, we analysed cellular transcriptional responses of cells to IAV M2 overexpression and identified RAB GTPase protein RAB33B as a key factor. RAB33B was significantly up-regulated by IAV M2 and promoted IAV replication by enhancing autophagy. We further found that autophagy regulates the interaction of IAV M2, RAB33B, and LC3, facilitating M2 membrane trafficking through autophagic-like vesicles. In addition, ATG16L1 (an effector of RAB33B) and TBC1D25 (a GTPase-activating protein for RAB33B) contributed to IAV M2-induced autophagy, thereby affecting viral replication. Collectively, our findings reveal a novel mechanism in which RAB33B is essential for IAV M2 trafficking to the plasma membrane, facilitating viral replication through enhanced autophagy. These insights shed new light on the autophagy-based cellular transport mechanisms of IAV M2 and highlight potential antiviral targets.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"56 1","pages":"129"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12219998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}