Virulence最新文献

{"title":"Guanosine enhances the bactericidal effect of ceftiofur sodium on <i>Streptococcus suis</i> by activating bacterial metabolism.","authors":"Yue Dong, Xiaona Liu, Shanshan Xiong, Mingyu Cao, Haojie Wu, Long Chen, Mengmeng Zhao, Yadan Zheng, Zhiyun Zhang, Yanyan Liu, Yanhua Li, Qianwei Qu, Chunliu Dong","doi":"10.1080/21505594.2025.2453525","DOIUrl":"10.1080/21505594.2025.2453525","url":null,"abstract":"<p><p>The emergence and rapid development of antibiotic resistance poses a serious threat to global public health. <i>Streptococcus suis</i> (<i>S. suis</i>) is an important zoonotic pathogen, and the development of its antibiotic resistance has made the infections difficult to treat. The combination of non-antibiotic compounds with antibiotics is considered a promising strategy against multidrug-resistant bacteria. However, the mechanism by which metabolites act as antibiotic adjuvant remains unclear. Here, we found that guanosine metabolism was repressed in multidrug-resistant <i>S. suis</i>. Exogenous guanosine promoted the antibacterial effects of ceftiofur sodium (CEF) <i>in vitro</i> and <i>in vivo</i>. Furthermore, we demonstrated that exogenous guanosine promoted the biosynthesis of purine pathway, TCA cycle and bacterial respiration, which make bacteria more sensitive to the killing effect of antibacterial. In addition, the function of the cell membrane is affected by guanosine and the accumulation of antimicrobials in the bacteria increased. Bacterial-oxidative stress and DNA damage induced by guanosine is also one of the mechanisms by which the antibacterial effect is enhanced. These results suggest that guanosine is a promising adjuvant for antibacterial drugs and provide new theoretical basis for the clinical treatment of <i>S. suis</i> infection.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2453525"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366166","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":"In vitro co-culture of <i>Fasciola hepatica</i> newly excysted juveniles (NEJs) with 3D HepG2 spheroids permits novel investigation of host-parasite interactions.","authors":"Aiste Vitkauskaite, Emma McDermott, Richard Lalor, Carolina De Marco Verissimo, Mahshid H Dehkordi, Kerry Thompson, Peter Owens, Howard Oliver Fearnhead, John Pius Dalton, Nichola Eliza Davies Calvani","doi":"10.1080/21505594.2025.2482159","DOIUrl":"10.1080/21505594.2025.2482159","url":null,"abstract":"<p><p><i>Fasciola hepatica</i>, or liver fluke, causes fasciolosis in humans and livestock. Following ingestion of vegetation contaminated with encysted parasites, metacercariae, newly excysted juveniles (NEJ) excyst in the small intestine and cross the intestinal wall. After penetrating the liver, the parasite begins an intra-parenchymal migratory and feeding phase that not only drives their rapid growth and development but also causes extensive haemorrhaging and immune pathology. Studies on infection are hindered by the difficulty in accessing these microscopic juvenile parasites <i>in vivo</i>. Thus, a simple and scalable <i>in vitro</i> culture system for parasite development is needed. Here, we find that two-dimensional (2D) culture systems using cell monolayers support NEJ growth to a limited extent. By contrast, co-culture of <i>F. hepatica</i> NEJ with HepG2-derived 3D spheroids, or \"mini-livers,\" that more closely mimic the physiology and microenvironment of <i>in vivo</i> liver tissue, promoted NEJ survival, growth, and development. NEJ grazed on the peripheral cells of the spheroids, and they released temporally regulated digestive cysteine proteases, FhCL3, and FhCL1/2, similar to <i>in vivo</i> parasites. The 3D co-culture induced development of the NEJ gut and body musculature, and stimulated the tegument to elaborate spines and a variety of surface sensory/tango/chemoreceptor papillae (termed S1, S2, and S3); these were especially pronounced around the oral and ventral suckers that sense host chemical cues and secure the parasite in tissue. HepG2 3D spheroid/parasite co-culture methodologies should accelerate investigations into the understanding of <i>F. hepatica</i> NEJ developmental biology and studies on host-parasite interactions, and streamline the search for new anti-parasite interventions.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2482159"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711454","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":"Tamdy virus pathogenesis in immunocompetent and immunocompromised mouse models.","authors":"Mingxue Cui, Hua-Chen Zhu, Xiurong Wang, Ying Cao, Di Liu, Michael J Carr, Yi Guan, Hong Zhou, Weifeng Shi","doi":"10.1080/21505594.2025.2503457","DOIUrl":"10.1080/21505594.2025.2503457","url":null,"abstract":"<p><p>Tamdy virus (TAMV) is one of the zoonotic tick-borne bunyaviruses that have emerged as global public health threats in recent decades. To date, however, TAMV pathogenesis remains poorly understood. In the present study, we have established different mouse infection models to enable investigation of TAMV pathogenesis. Adult BALB/c mice did not exhibit obvious clinical symptoms or signs post-TAMV infection. In contrast, adult type I interferon receptor knockout (IFNAR^-/-) A129 mice were found to be susceptible to high-doses of TAMV (6 × 10² and 6 × 10⁴ FFU) and all developed severe clinical symptoms and signs, including weight loss and immobility, and reached the euthanasia criteria at 4/5-day post-infection (dpi). Viral RNA was detected in peripheral blood and different tissues (heart, liver, spleen, lung, kidney, intestine, and brain) of the high-dose infected adult A129 mice, with the highest viral loads in the liver (approximately 10^8.3 copies/μL). Pathological examination also revealed severe liver damage in the high-dose infected A129 mice. In addition, the titres of TAMV-specific IgM and IgG antibodies increased rapidly 4-5 dpi. Analysis of cytokine and chemokine expression changes demonstrated that type I IFN may play an important role in the host defence against viral infection by enhancing IL-10 production. Gene ontology and KEGG analyses showed that liver injury may be associated with virus-induced expression of inflammatory cytokines and chemokines. Together, we have investigated TAMV pathogenesis using immunocompetent and immunocompromised mouse models, which will facilitate the development of TAMV-specific antivirals and vaccines.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2503457"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998572","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":"Circulation characteristics of bat coronaviruses linked to bat ecological factors in Korea, 2021-2022.","authors":"Min Chan Kim, Seong Sik Jang, Thi Van Lo, Ji Yeong Noh, Hyun A Lim, Ha Yeon Kim, Da Young Mun, Kihyun Kim, Taek-Woo Lee, Yong Gun Choi, Sun-Woo Yoon, Dae Gwin Jeong, Sun-Sook Kim, Hye Kwon Kim","doi":"10.1080/21505594.2025.2502551","DOIUrl":"10.1080/21505594.2025.2502551","url":null,"abstract":"<p><p>Considering that bat ecology alterations may be linked with pathogen spillover, research on bat coronaviruses, particularly on the infection and transmission pattern among bats in relation with their ecology, is essential. We captured bats distributed in Korea from 2021 to 2022, examined coronaviruses in oral swabs, feces, urine, and ectoparasites, and were able to detect alphacoronavirus. We investigated coronaviruses, but noted no substantial differences in the body condition index in the coronavirus-positive bats. Binary logistic regression analysis revealed that bat ecological factors that were significantly associated with coronavirus-positive were roost type, sample type, and bat species. Coronavirus-positive ectoparasite cases suggested additional study on the potential role of them as the viral transmission vectors or fomites. Reinfection of a different coronavirus in recaptured bats was evident, suggesting the possibility that coronavirus circulation can evade the potential protective immunity acquired from previous coronavirus infections. The present findings provide comprehensive information on the coronaviruses transmission dynamics within bat populations linked with bat ecology.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2502551"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021231","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 small RNA from <i>Streptococcus suis</i> epidemic ST7 strain promotes bacterial survival in host blood and brain by enhancing oxidative stress resistance.","authors":"Zijing Liang, Shuoyue Wang, Xinchi Zhu, Jiale Ma, Huochun Yao, Zongfu Wu","doi":"10.1080/21505594.2025.2491635","DOIUrl":"10.1080/21505594.2025.2491635","url":null,"abstract":"<p><p><i>Streptococcus suis</i> is a Gram-positive pathogen causing septicaemia and meningitis in pigs and humans. However, how <i>S. suis</i> maintains a high bacterial load in the blood and brain is poorly understood. In this study, we found that a small RNA rss03 is predominantly present in <i>S. suis</i>, <i>Streptococcus parasuis</i>, and <i>Streptococcus ruminantium</i>, implying a conserved biological function. rss03 with a size of 303 nt mainly exists in <i>S. suis</i> sequence type (ST) 1 and epidemic ST7 strains that are responsible for human infections in China. Using MS2-affinity purification coupled with RNA sequencing (MAPS), proteomics analysis, and CopraRNA prediction, 14 direct targets of rss03 from an ST7 strain were identified. These direct targets mainly involve substance transport, transcriptional regulation, rRNA modification, and stress response. A more detailed analysis reveals that rss03 interacts with the coding region of <i>glpF</i> mRNA, and unexpectedly rss03 protects <i>glpF</i> mRNA from degradation by RNase J1. The GlpF protein is an aquaporin, contributes to <i>S. suis</i> oxidative stress resistance by H₂O₂ efflux, and facilitates bacterial survival in murine macrophages RAW264.7. Finally, we showed that rss03 and GlpF are required to maintain a high bacterial load in mouse blood and brain. Our study presents the first sRNA targetome in streptococci, enriches the knowledge of sRNA regulation in streptococci, and identifies pathways contributing to <i>S. suis</i> pathogenesis.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2491635"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037358","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 relationship between HERVs and exogenous viral infections: A focus on the value of HERVs in disease prediction and treatment.","authors":"Anhua Dou, Juan Xu, Chenglin Zhou","doi":"10.1080/21505594.2025.2523888","DOIUrl":"10.1080/21505594.2025.2523888","url":null,"abstract":"<p><p>Human endogenous retroviruses (HERVs) are virus-related sequences that are a normal part of the human genome; they account for about 8% of the human genome. Reactivation of these ancestral proviral sequences can lead to the generation of functional products. Several reactivated HERVs are associated with cancer and autoimmune diseases. Emerging research suggests that reactivated HERVs may play a significant role in the development of viral diseases such as acquired immune deficiency syndrome (AIDS) and coronavirus disease 2019 (COVID-19), as well as in neuroinflammatory diseases possibly triggered by viral factors, such as multiple sclerosis (MS). Studies exploring the relationship between HERVs and exogenous viral infections have the potential to offer a fresh perspective on developing treatment and prevention strategies for exogenous viral infections. The mechanism of the transactivation of HERVs caused by exogenous viral infection, as well as the contribution of HERVs to viral diseases or diseases triggered by viral factors, deserve further research. Here, we review the relationship between exogenous viruses and HERVs in several common diseases caused or triggered by viral infections, with a focus on the value of HERVs as biomarkers for forecasting disease advancement or prognosis and as potential targets for therapeutic interventions.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2523888"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545091","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":"Comparison of Omicron and respiratory virus infections in pediatric liver transplantation: Impact of perioperative identification status.","authors":"Pingbo Jin, Weili Wang, Wei Zhang, Xin Duan, Li Wang, Lei Zeng, Rongrong Wang, Xinyu Yu, Ying Chen, Yigang Qian, Min Zhang, Yan Shen, Xueli Bai, Tingbo Liang","doi":"10.1080/21505594.2025.2525929","DOIUrl":"10.1080/21505594.2025.2525929","url":null,"abstract":"<p><p>Peri-operative respiratory virus (RV) infection is critical in paediatric liver transplantation. However, it has been inadequately studied, especially in terms of the clinical latency of infection (incubation period) and Omicron variant infection. Herein, we compared the infection profile of common RVs and Omicron variants in paediatric liver transplantation, aiming to identify the association of virus infection with outcomes. The Omicron cohort was designed prospectively, and the RV cohort was retrospective. Survival outcomes, medical resources, and major complications were compared. Risk factors associated with peri-operative mortality were investigated using regression analysis. We enrolled 649 paediatric liver transplantation patients, including 28 Omicron and 61 RV infections. The 1-y overall survival was 97.7 ± 0.6% for the non-infected group, and 93.4 ± 3.2% for the RV group (<i>p</i> = 0.092). No death occurred in the Omicron group. Mortality was higher in the clinical latency infection group compared with that in the non-infected group (13.8% <i>vs</i>. 1.4%, <i>p</i> = 0.002). Latent RV infection (hazard ratio (HR) = 6.323, 95% confidence interval (CI): 1.374-29.087), Multi‑drug resistance organism pneumonia (HR = 7.177, 95% CI: 1.817-28.350), infectious shock (HR = 4.284, 95% CI: 0.995-18.442) and blood loss (HR = 3.209, 95% CI: 1.166-8.833) were independent risk factors for peri-operative mortality. In conclusion, pre-transplant viral screening is fundamental to paediatric liver transplantation. Peri-operative Omicron infection might be controllable, while RV infection led to more complications compared with those in the non-infected group. Clinical latency infection is the key risk for paediatric liver transplantation mortality.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2525929"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576437","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":"Comprehensive analysis of human keratinocyte interactions with <i>Candida albicans</i> and <i>Candida parapsilosis</i>.","authors":"Ádám Novák, Erik Zajta, Máté Csikós, Emese Halmos, Márton Horváth, Orsolya Tildy, András Szekeres, Gergő Svorenj, Nikolett Gémes, Gábor J Szebeni, Renáta Tóth, Attila Gácser","doi":"10.1080/21505594.2025.2532815","DOIUrl":"10.1080/21505594.2025.2532815","url":null,"abstract":"<p><p>In recent years, microbiome studies have revealed that <i>Candida</i> species are common colonizers of the human skin. The distribution of species, however, varies greatly. Although <i>C. parapsilosis</i> is more likely to resemble skin commensals, opinions are divided, and discrepancies are present regarding <i>C. albicans</i> that is also often associated with cutaneous candidiasis. Therefore, we aimed to thoroughly assess the nature of skin epithelial cell - <i>Candida</i> interactions. To study species-specific host responses, we examined internalization, cytokine and metabolic responses in different keratinocytes (HaCaT, HPV-KER) along with host cell damage following fungal stimuli. To rigorously examine yeast-keratinocyte interactions, we applied two distinct isolates of both <i>C. albicans</i> (SC5314, WO-1) and <i>C. parapsilosis</i> (GA1, CLIB214). Comparison of the two fungi's virulence revealed that while <i>C. albicans</i> effectively adheres to human keratinocytes and causes subsequent damage, <i>C. parapsilosis</i> is unable to establish lasting physical contact and causes less harm. In terms of keratinocyte response, both cell lines showed significantly enhanced cellular (internalization), humoral (IL-6, IL-8) and metabolic responses (2-ketoglutaric acid, citric acid, threorine, hypotaurine) to <i>C. albicans</i> strains, while those towards <i>C. parapsilosis</i> remained relatively low or similar to the control condition. Under certain conditions strain preference was also detected. Of the two cell lines, HPV-KER was more sensitive, as besides interspecies differences, intraspecies differences were also measurable. These results suggest that <i>C. albicans</i> triggers an enhanced antifungal response, thus does not closely resemble skin commensals, like <i>C. parapsilosis</i>. Furthermore, HPV-KER might serve as a more applicable tool for studying keratinocyte antifungal responses.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":" ","pages":"2532815"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643653","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":"Senecavirus a can replicate in apical-out porcine intestinal organoids and induce stress granules and innate immune response.","authors":"Ying Wang, Zhiying Wei, Jiaxuan Li, Xiaona Wang, Yanping Jiang, Wen Cui, Zhifu Shan, Lijie Tang","doi":"10.1080/21505594.2025.2548623","DOIUrl":"https://doi.org/10.1080/21505594.2025.2548623","url":null,"abstract":"<p><p>Senecavirus A (SVA) causes clinical blistering and ulcerative lesions resembling foot-and-mouth disease (FMD), often with mixed infections that exacerbate the disease and impact pig industry development. SVA has been demonstrated to induce diarrhea, dehydration and mortality in piglets. However, the underlying mechanisms of SVA-related intestinal infections remain underexplored. In this study, a three-dimensional cultured apical-out porcine intestinal organoid model was constructed, comprising a variety of cell types, including intestinal stem cells, enterocytes, goblet cells, proliferative cells, Paneth cells and enteroendocrine cells. The model demonstrated SVA susceptibility in intestinal epithelial cells through cytopathic effects, viral detection, and replication. The results revealed an infection sequence from enterocytes to enteroendocrine cells, Paneth cells and intestinal stem cells and ultimately to proliferating cells, which identified enterocytes as the primary SVA targets. The presence of stress granules was observed at 4 hours post-infection (hpi), with a notable decline over time, reaching near-disappearance at 20 hpi. At this stage, an innate immune response was evident, with significant upregulation of the interferon IFN-α, the interferon-stimulated gene ISG-15, OAS1, OAS2, the signal transducer and activator of transcription 1 (STAT1), the mucosal immunity gene Muc2, and the cytokine IL-6, which appeared to limit further SVA infection. This study elucidates the infection pattern of SVA in intestinal epithelial cells and reveals the mechanism of interaction. It offers insights for controlling secondary infections.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2548623"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971080","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":"PRRSV evades innate immune cGAS-STING antiviral function via its Nsp5 to deter STING translocation and activation.","authors":"Yulin Xu, Chenglin Chi, Qihang Xin, Jiang Yu, Yuyu Zhang, Pingping Zhang, Wangli Zheng, Sen Jiang, Wanglong Zheng, Nanhua Chen, Jiaqiang Wu, Jianzhong Zhu","doi":"10.1080/21505594.2025.2548625","DOIUrl":"https://doi.org/10.1080/21505594.2025.2548625","url":null,"abstract":"<p><p>Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is an important pathogen that seriously endangers pig breeding, causing significant economic losses to the global swine industry. Our previous study found that the DNA sensing innate cGAS-STING signaling pathway plays an important role in inducing interferon (IFN) upon PRRSV infection and inhibition of PRRSV replication. However, the mechanism underlying immune evasion by PRRSV remains unclear. In the current study, we found that PRRSV non-structural protein 5 (Nsp5) strongly inhibits the cGAS-STING-IFN antiviral response. Furthermore, we found that Nsp5 interacts with STING, blocking STING transport from the ER to the Golgi apparatus and interfering with STING recruitment of TBK1/IKKε/IRF3. Finally, we demonstrated that the Nsp5 36-47 and 58-67 amino acid regions are critical for inhibiting STING activity and PRRSV replication. This study describes a novel mechanism by which PRRSV suppresses the host innate antiviral response and has implications for our understanding of PRRSV pathogenesis.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2548625"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971082","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}