Veterinary microbiology最新文献

{"title":"Capsular immunity is necessary for protection against some but not all strains of Glaesserella parasuis","authors":"Samantha J. Hau ,&nbsp;Shi-Lu Luan ,&nbsp;Lucy A. Weinert ,&nbsp;Paul R. Langford ,&nbsp;Andrew Rycroft ,&nbsp;Brendan W. Wren ,&nbsp;Duncan J. Maskell ,&nbsp;Alexander W. (Dan) Tucker ,&nbsp;Susan L. Brockmeier","doi":"10.1016/j.vetmic.2025.110509","DOIUrl":"10.1016/j.vetmic.2025.110509","url":null,"abstract":"<div><div><em>Glaesserella parasuis</em> is the causative agent of Glässer’s disease in pigs and results in significant losses to the swine industry annually. Due to the serovar and strain specific response associated with many bacterin vaccines, there has been difficulty generating broad heterologous protection. Here, an unencapsulated <em>G. parasuis</em> mutant (HS069∆cap) was assessed as a bacterin vaccine and compared to a bacterin made from the encapsulated parent strain, against challenge with the homologous, parent strain (serovar 5) as well as four heterologous challenge strains (serovar 1, 4, 5, and 14). Both the HS069 and HS069∆cap bacterins generated high titers to the homologous and heterologous strains. The HS069∆cap bacterin was able to provide protection against the parent strain as well as 12939 (serovar 1), 2170B (serovar 4), and MN-H (serovar 13), but was unable to protect animals from challenge with Nagasaki (serovar 5). In contrast, the HS069 bacterin was able to provide protection against all challenge strains, showing the importance of serovar specific immunity against the challenge strain Nagasaki. This appears to be due to the production of a more abundant and well-organized capsule in Nagasaki as compared to HS069. This study indicates HS069∆cap is a good candidate strain for bacterin development; however, it may be less able to provide protection against highly encapsulated strains of <em>G. parasuis</em>.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110509"},"PeriodicalIF":2.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDAC4 suppresses porcine epidemic diarrhea virus infection through negatively regulating MEF2A-GLUT1/3 axis- mediated glucose uptake","authors":"Xiaomin Wang ,&nbsp;Lei Wang ,&nbsp;Duan Li ,&nbsp;Yilong Liu ,&nbsp;Qi Shang ,&nbsp;Yanling Liu ,&nbsp;Leyi Zhang ,&nbsp;Zheng Xu ,&nbsp;Cuiqin Huang ,&nbsp;Changxu Song","doi":"10.1016/j.vetmic.2025.110520","DOIUrl":"10.1016/j.vetmic.2025.110520","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV), a porcine enteropathogenic coronavirus, causes severe diarrhea and death in neonatal piglets. Histone deacetylase 4 (HDAC4), a member of class IIa deacetylases, controls a wide range of physiological processes, but, little is known about its role in PEDV infection. Here, we report a novel strategy by which PEDV manipulates HDAC4. First, HDAC4 expression was examined, and showed a significant down-regulation in PEDV-infected Vero and IPEC-J2 cells. Subsequently, knockdown of HDAC4 by specific small interfering RNA (siRNA) led to an increase in viral infection, whereas overexpression of HDAC4 remarkably suppressed PEDV infection. Mechanistically, we showed that HDAC4 significantly reduced glucose uptake, as glucose is required for PEDV infection. Through screening, we identified glucose transporters 1 and 3 (GLUT1 and GLUT3) as responsible for glucose uptake during PEDV infection. We further confirmed that HDAC4 regulated GLUT1 and GLUT3 expression through its converging hub, myocyte enhancer factor 2 A (MEF2A). Taken together, these findings contribute to a better understanding of a novel function of HDAC4 in regulating glucose uptake via MEF2A-GLUT1/3 to limit PEDV infection, and provide new strategies for the development of anti-PEDV drugs.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110520"},"PeriodicalIF":2.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surface expression of PEDV nucleocapsid protein facilitates NK cell-mediated ADCC via anti-N nonneutralizing antibody","authors":"Xiang Liu ,&nbsp;Meng Zhang ,&nbsp;Yi Luo ,&nbsp;Shijie Yan ,&nbsp;Haoran Xu ,&nbsp;Yao Yao ,&nbsp;Farong Xu ,&nbsp;Pinghuang Liu","doi":"10.1016/j.vetmic.2025.110518","DOIUrl":"10.1016/j.vetmic.2025.110518","url":null,"abstract":"<div><div>The nucleocapsid (N) protein is the most abundant viral protein during porcine epidemic diarrhea virus (PEDV) infection and exhibits strong immunogenicity, prompting the host immune system to produce large quantities of antibodies against it. However, N-specific antibodies are non-neutralizing, as the N protein is typically located inside viral particles. Understanding the roles of N-specific antibodies during PEDV infection is crucial for developing more effective vaccines. In this study, we demonstrated that a significant amount of PEDV-N protein is expressed on the surface of living cells during PEDV infection or transient N expression. Mechanistically, the PEDV-N protein may reach the cell surface via the exosome secretion pathway. Furthermore, anti-N antibodies can bind to the surface N protein and induce antibody-dependent natural killer (NK) cell-mediated cytotoxicity (ADCC), directly killing PEDV-infected cells. Although anti-N antibodies lack neutralizing effects against PEDV infection, they can target the N protein present on the surface of PEDV-infected cells to induce NK cell-mediated ADCC, thus protecting the host from viral infection. Our results indicate that the N protein holds significant potential as a candidate for designing vaccines against porcine enteric viruses.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110518"},"PeriodicalIF":2.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGEV NSP1 enhances viral replication through antagonizing stress granule formation","authors":"Yutong Tang,&nbsp;Yue Zhang,&nbsp;Ning Yang,&nbsp;Han Shi,&nbsp;Yuguang Fu,&nbsp;Bingrong Bai,&nbsp;Baoyu Li,&nbsp;Bin Yang,&nbsp;Guangliang Liu","doi":"10.1016/j.vetmic.2025.110502","DOIUrl":"10.1016/j.vetmic.2025.110502","url":null,"abstract":"<div><div>Stress granules (SGs) are membrane-less organelles that form in response to adverse external stimuli. Upon viral invasion, SGs formation can serve as a cellular defence mechanism against infection. Transmissible gastroenteritis virus (TGEV), an <em>α</em>-coronavirus with a large positive-sense single-stranded RNA genome, causes diarrhoea, vomiting, dehydration, and even fatality in piglets. Previous studies have shown that coronaviruses employ various strategies to inhibit the SGs formation, thereby facilitating viral replication. However, the interplay between TGEV infection and the SGs formation remains unclear. In this study, we demonstrate that the SGs formation can enhance antiviral innate immunity mediated through the retinoic acid-inducible gene I (RIG-I) signaling pathway, thereby inhibiting TGEV replication. Nevertheless, TGEV counteracts the SGs formation by reducing the protein level of Ras-GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) to promote its own replication. Among the TGEV-encoded proteins, non-structural protein 1 (NSP1) exhibits the strongest inhibitory effect on the SGs formation. In summary, our study systematically elucidated the relationship between TGEV and the SGs formation, providing insights into the mechanism of TGEV pathogenesis and a theoretical foundation for identifying novel anti-coronavirus targets.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110502"},"PeriodicalIF":2.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular epidemiology, immunobiology, genomics and proteomics insights into bovine brucellosis","authors":"Y.K. Prabhakar,&nbsp;Somy Skariah,&nbsp;G. Shanmugam,&nbsp;Rajeswari Shome","doi":"10.1016/j.vetmic.2025.110505","DOIUrl":"10.1016/j.vetmic.2025.110505","url":null,"abstract":"<div><div><em>Brucella</em> species are intracellular Gram-negative bacteria that cause brucellosis, a global zoonosis that impacts cattle productivity and public health. Both cattle and buffaloes are susceptible to bovine brucellosis, which can lead to severe degenerative changes in uterine mucosa of non-pregnant animals, including ulcerative endometritis and fibrosis. Vasculitis, localized coagulative necrosis, and ulceration of the uterine mucosa have all been reported in pregnant animals. Male testicles get inflamed due to <em>Brucella</em>, which results in infertility. This review article covers the molecular epidemiology, pathophysiology, immunobiology, genomics, and proteomics of <em>Brucella</em>, with an emphasis on novel discoveries and more recent research, especially on bovine brucellosis. The integration of molecular pathology and sero-prevalence data provide the insights into epidemiology, transmission dynamics, and genetic diversity of bovine brucellosis. The immunobiological response studies of brucellosis have provided insights into the tactics employed by <em>Brucella</em> to infect host cells and elude immune responses. Proteomics was utilized to find biomarkers for both acute and chronic brucellosis, which resulted in the identification of proteins with differential expression linked to immune response, inflammation, and extracellular matrix modulation. The genetic diversity, virulence factors, and evolution of <em>Brucella</em> strains were mostly investigated using genomics. The genomic makeup and architecture of <em>Brucella</em> isolates were examined using whole-genome sequencing, which revealed genetic markers linked to pathogenicity and drug resistance. This review provides possible treatment targets, diagnostic biomarkers, and vaccine candidates, contributing to molecular understanding of bovine brucellosis.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110505"},"PeriodicalIF":2.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol-dependent Nsp5-endosomes co-trafficking to lysosomes facilitates porcine reproductive and respiratory syndrome virus replication by activating autophagy","authors":"Haoxin Dong ,&nbsp;Qiming Pei ,&nbsp;Jiahui Ren ,&nbsp;Yaci Zhang ,&nbsp;Xuedan Wei ,&nbsp;Aijuan Shen ,&nbsp;Yunshuo Lu ,&nbsp;Ziheng Zhang ,&nbsp;Yongkun Du ,&nbsp;Guoqing Zhuang ,&nbsp;Angke Zhang ,&nbsp;Hong Duan","doi":"10.1016/j.vetmic.2025.110507","DOIUrl":"10.1016/j.vetmic.2025.110507","url":null,"abstract":"<div><div>Our previous studies showed that intracellular endosomal vesicles participated in PRRS virions trafficking in the early stage of viral infection, and cholesterol retention in endosomal vesicles disturbed viral replication via blocking PRRSV-endosomal vesicles membrane fusion. However, whether endosomal vesicles were associated with PRRSV protein(s) trafficking and the role of cholesterol in this process was still unclarity. In this study, we sought to elucidate the mechanism of cholesterol in endosomal vesicles-mediated viral protein transportation. The results showed that endosomal vesicles participated in trafficking of PRRSV Nsp5 protein. After being synthesized in endoplasmic reticulum (ER) and Golgi apparatus, Nsp5 was trafficked to early endosomes (EEs), but not endocytic recycling compartments (ERCs), then to late endosomes (LEs), and eventually reached lysosomal compartments, whereas disruption of cholesterol flux or LEs function led to the inability of Nsp5 arriving at lysosomes, where Nsp5 activated cellular autophagy to promote PRRSV replication. Molecular docking predictions revealed that cholesterol could form two hydrogen bonds with 74 alanine and 78 asparagine of Nsp5. After mutating the aforementioned binding sites, the replication efficiency of PRRSV decreased. Subsequently, the role of cholesterol in PRRSV replication was explored. Blocking of cholesterol flux significantly inhibited PRRSV replication. Single virus infection cycle analysis showed that cholesterol flux disorder did not affect virus adsorption, but could inhibit virus entry into host cells and block EEs-LEs-lysosomes mediated trafficking of virions, leading to virions retention in endosomal compartments. The present studies suggest that cholesterol and endosomal vesicles synergistically participate in Nsp5 trafficking to promote PRRSV replication, which may provide new insights for the development of novel antiviral drugs targeting cholesterol metabolism pathways or the improvement of commercial vaccines.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110507"},"PeriodicalIF":2.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-B-cell cloning and recombinant antibodies generation to analyze the antigenicity of porcine reproductive and respiratory syndrome virus nonstructural protein 12","authors":"Hongyong Duan ,&nbsp;Chaozhi Tang ,&nbsp;Song Han ,&nbsp;Nan Yang ,&nbsp;Shumao Wang ,&nbsp;Fei Gao ,&nbsp;Yanjun Zhou ,&nbsp;Guangzhi Tong ,&nbsp;Kuan Zhao ,&nbsp;Liwei Li","doi":"10.1016/j.vetmic.2025.110506","DOIUrl":"10.1016/j.vetmic.2025.110506","url":null,"abstract":"<div><div>The prevalence and variation of porcine reproductive and respiratory syndrome virus (PRRSV) in China are increasing. The rapid preparation of essential antibodies will effectively reveal the antigenicity, epitopes, and intracellular distribution of viral proteins. Single-B-cell antibody technology is a novel method for screening diverse functional monoclonal antibodies (mAbs). Herein, we successfully expressed PRRSV nonstructural protein 12 (Nsp12) in suspension-cultured Chinese hamster ovary (CHO) cells. Using single-B-cell antibody technology, we utilized fluorescence-activated cell sorting to collect individual immune B cells and prepared single-cell reverse transcription-polymerase chain reaction to clone the variable region of immunoglobulin heavy chain (<em>IgH</em>) and immunoglobulin light chain (<em>IgK</em>). Two recombinant mAbs were generated via transient transfection of CHO cells with the corresponding expression plasmids of IgH and IgK. A novel linear epitope (¹⁰⁴YEFTGNGEDW¹¹³) of Nsp12 was identified using mAb_1N14. This epitope was conserved in lineages 1, 5, and 8 of PRRSV-2 and was located on the surface of the Nsp12 spatial structure. The amino acid mutation in Nsp12 of lineage 3 PRRSV-2 affected the antigenicity of this linear epitope. A conserved conformational epitope was identified using mAb_2S18, and the spatial structure of Nsp12 showed high similarity between PRRSV-1 and different lineages of PRRSV-2. During PRRSV infection, Nsp12 was distributed in the cytoplasm and accumulated in the nucleus. Overall, antigenicity analysis and novel epitope identification contributed to the in-depth exploration of the biological function of Nsp12 and will facilitate the development of detection assays and antiviral strategies.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"304 ","pages":"Article 110506"},"PeriodicalIF":2.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid nanoparticle-encapsulated DNA vaccine encoding African swine fever virus p54 antigen elicits robust immune responses in pigs","authors":"Danh C. Lai ,&nbsp;The N. Nguyen ,&nbsp;Korakrit Poonsuk ,&nbsp;D. Scott McVey ,&nbsp;Hiep L.X. Vu","doi":"10.1016/j.vetmic.2025.110508","DOIUrl":"10.1016/j.vetmic.2025.110508","url":null,"abstract":"<div><div>African swine fever virus (ASFV) is one of the most significant viral pathogens affecting swine production worldwide. While several live attenuated ASF vaccines have been approved for clinical application in certain countries, there is a concern that the vaccine viruses might revert to virulence. Subunit vaccines containing one or a few viral immunogens provide a safer alternative. DNA plasmids are highly stable, easy to produce in large quantities at low cost, and safe for use in animals. However, unencapsulated DNA vaccines often exhibited low immunogenicity, largely due to the inefficient cellular entry of the plasmid DNA, leading to low protein expression. In this study, we used ASFV p54 as a model antigen to investigate the feasibility of using lipid nanoparticles (LNP) as nanocarriers to enhance the immunogenicity of DNA vaccines. Pigs immunized with the p54 LNP-DNA vaccine elicited high titers of p54-specific antibodies and T-cell responses after the second immunization. Using ELISAs based on an overlapping peptide library, we identified three antigenic areas within p54. Additionally, we noted that pigs vaccinated with the p54 LNP-DNA vaccine exhibited a similar antibody profile as those vaccinated with an experimental live attenuated vaccine or infected with a wild-type ASFV strain. The results highlight the promising potential of LNP-DNA as an effective platform for developing gene-based vaccines against ASFV.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110508"},"PeriodicalIF":2.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of recombinant CAV1-Fc in the treatment of ApxI toxin-induced damage by Actinobacillus pleuropneumoniae","authors":"Yaofang Hu ,&nbsp;Mengdi Zhang ,&nbsp;Gan Yang ,&nbsp;Haoran Guo ,&nbsp;Changsheng Jiang ,&nbsp;Pei Zhou ,&nbsp;Yanhong Chen ,&nbsp;Mengjia Zhang ,&nbsp;Ahmed H. Ghonaim ,&nbsp;Wentao Li ,&nbsp;Qigai He","doi":"10.1016/j.vetmic.2025.110504","DOIUrl":"10.1016/j.vetmic.2025.110504","url":null,"abstract":"<div><div>Currently, porcine contagious pleuropneumonia (PCP) caused by <em>Actinobacillus pleuropneumoniae</em> (APP), poses a significant threat to the pig breeding industry. There is an urgent need for effective therapeutic and prophylactic treatments, especially those that can overcome the limitations associated with vaccines and antibiotics. This includes the development of novel antitoxin agents, immunomodulatory therapies, and alternative strategies like phage therapy and herbal extracts. Our previous study has demonstrated membrane protein caveolin-1 (CAV1) is a key protein that acts as a functional receptor of APP ApxI toxin by binding to its acylated region. Here, we developed recombinant human N-CAV1-Fc fusion protein and C-CAV1-Fc fusion protein. Both fusion proteins could tightly bind to ApxI toxin. N-CAV1-Fc and C-CAV1-Fc fusion proteins efficiently blocked the interaction between ApxI toxin and immortalized porcine alveolar macrophages (iPAMs), thereby inhibiting cell apoptosis caused by APP ApxI toxin. Furthermore, prophylactic and therapeutic CAV1-Fc treatments effectively protected mice from ApxI toxin-induced damage, as determined by reduced weight loss, apoptosis factor transcription, and pathological changes in the lungs. The protective effects of N-CAV1-Fc and C-CAV1-Fc showed clear dose-dependent efficacy <em>in vivo</em>. Protein kinetics data indicated that N-CAV1-Fc has a relatively longer half-life <em>in vivo</em> compared to C-CAV1-Fc, making it an excellent candidate for prevention and treatment of APP infections.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110504"},"PeriodicalIF":2.4,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome profiling reveals that the host BRD4 protein facilitates African swine fever virus infection and suppresses inflammatory cytokine expression by downregulating transcriptional regulatory signaling pathways","authors":"Mengli Wu ,&nbsp;Jifei Yang ,&nbsp;Zhancheng Tian ,&nbsp;Hualin Sun ,&nbsp;Zhonghui Zhang ,&nbsp;Jianxun Luo ,&nbsp;Guiquan Guan ,&nbsp;Hong Yin ,&nbsp;Qingli Niu ,&nbsp;Rongzeng Hao","doi":"10.1016/j.vetmic.2025.110498","DOIUrl":"10.1016/j.vetmic.2025.110498","url":null,"abstract":"<div><div>The African swine fever virus (ASFV), a complex DNA virus belonging to the <em>Asfarviridae</em> family, is a significant threat to the global swine industry because of its high mortality rates and impact on international trade. The establishment of a stable and efficient cell culture model of ASFV <em>in vitro</em> is helpful for the development of effective vaccines. Several passaged cell lines supporting ASFV replication have been reported to meet the scientific purpose of serial passage of ASFV to a certain extent, but it remains to be determined whether gene expression is lost or whether immunogenicity changes after serial passage of the virus. It is also unclear these edited cell lines how to affect ASFV replication. In our previous study, 3D4/21 cells were transduced with a lentivirus packaging system to express the BD1/2 domain of bromodomain-containing protein 4 (BRD4-BD1/2) and establish a 3D4/21-BD1/2 cell line, which efficiently increased ASFV replication. In this study, the role of bromodomain-containing protein 4 (BRD4), particularly its BD1/2 domains,in enhancing ASFV replication was investigated using an engineered 3D4/21 cell line. Through RNA-Seq transcriptomic analysis, we revealed that the host BRD4 protein facilitates ASFV infection and suppresses key transcription factors (CDK9 and p-CDK9) and inflammatory cytokine expression by downregulating transcriptional regulatory signaling pathways and suppressing innate immune responses. This dual mechanism of BRD4-BD1/2 in promoting ASFV immune evasion and adaptation underscores the virus’s strategic exploitation of host epigenetic factors. These findings provide valuable insights into viral pathogenesis and identify potential therapeutic targets, paving the way for future antiviral strategies.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"305 ","pages":"Article 110498"},"PeriodicalIF":2.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}