{"title":"Duck hepatitis A virus utilizes PCBP2 to facilitate viral translation and replication","authors":"Chenxia Xu, Yurui Jiang, Mingshu Wang, Anchun Cheng, Wei Zhang, Xumin Ou, Di Sun, Qiao Yang, Ying Wu, Bin Tian, Yu He, Zhen Wu, Shaqiu Zhang, Xinxin Zhao, Juan Huang, Dekang Zhu, Shun Chen, Mafeng Liu, Renyong Jia","doi":"10.1186/s13567-024-01369-9","DOIUrl":"https://doi.org/10.1186/s13567-024-01369-9","url":null,"abstract":"Duck hepatitis A virus type 1 (DHAV-1) is an important member of the Picornaviridae family that causes highly fatal hepatitis in ducklings. Since picornaviruses have small genomes with limited coding capacity, they must utilize host proteins for viral cap-independent translation and RNA replication. Here, we report the role of duck poly(rC)-binding protein 2 (PCBP2) in regulating the replication and translation of DHAV-1. During DHAV-1 infection, PCBP2 expression was upregulated. A biotinylated RNA pull-down assay revealed that PCBP2 positively regulates DHAV-1 translation through specific interactions with structural domains II and III of the DHAV-1 internal ribosome entry site (IRES). Further studies revealed that PCBP2 promotes DHAV-1 replication via an interaction of its KH1 domain (aa 1–92) with DHAV-1 3Dpol. Thus, our studies demonstrated the specific role of PCBP2 in regulating DHAV-1 translation and replication, revealing a novel mechanism by which host‒virus interactions regulate viral translation and replication. These findings contribute to further understanding of the pathogenesis of picornavirus infections.","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"41 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matteo Cuccato, Sara Divari, Diana Giannuzzi, Cristina Grange, Riccardo Moretti, Andrea Rinaldi, Christine Leroux, Paola Sacchi, Francesca Tiziana Cannizzo
{"title":"Extracellular vesicle miRNome during subclinical mastitis in dairy cows","authors":"Matteo Cuccato, Sara Divari, Diana Giannuzzi, Cristina Grange, Riccardo Moretti, Andrea Rinaldi, Christine Leroux, Paola Sacchi, Francesca Tiziana Cannizzo","doi":"10.1186/s13567-024-01367-x","DOIUrl":"https://doi.org/10.1186/s13567-024-01367-x","url":null,"abstract":"Bovine mastitis is one of the main inflammatory diseases that can affect the udder during lactation. Somatic cell counts and sometimes microbiological tests are routinely adopted during monitoring diagnostics in dairy herds. However, subclinical mastitis is challenging to identify, reducing the possibility of early treatments. The main aim of this study was to investigate the miRNome profile of extracellular vesicles isolated from milk as potential biomarkers of subclinical mastitis. Milk samples were collected from a total of 60 dairy cows during routine monitoring tests. Small RNA sequencing technology was applied to extracellular vesicles of milk samples collected from cows classified according to the somatic cell count to identify differences in the miRNome between mastitic and healthy cows. A total of 1997 miRNAs were differentially expressed between both groups. Among them, 68 miRNAs whose FDRs were < 0.05 were mostly downregulated, with only one upregulated miRNA (i.e., miR-361). Functional analysis revealed that miR-455-3p, miR-503-3p, miR-1301-3p and miR-361-5p are involved in the regulation of several biological processes related to mastitis, including immune system-related processes. This study suggests the involvement of extracellular vesicle-derived miRNAs in the regulation of mastitis. Moreover, these findings provide evidence that miRNAs from milk extracellular vesicles can be used to identify biomarkers of mastitis. However, further studies must be conducted to validate these miRNAs, especially for subclinical diagnosis.","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"25 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thibaut Morel-Journel, Pauline Ezanno, Elisabeta Vergu
{"title":"Rewiring cattle movements to limit infection spread","authors":"Thibaut Morel-Journel, Pauline Ezanno, Elisabeta Vergu","doi":"10.1186/s13567-024-01365-z","DOIUrl":"https://doi.org/10.1186/s13567-024-01365-z","url":null,"abstract":"Cattle tracing databases have become major resources for representing demographic processes of livestock and assessing potential risk of infections spreading by trade. The herds registered in these databases are nodes of a network of commercial movements, which can be altered to lower the risk of disease transmission. In this study, we develop an algorithm aimed at reducing the number of infected animals and herds, by rewiring specific movements responsible for trade flows from high- to low-prevalence herds. The algorithm is coupled with a generic computational model based on the French cattle movement tracing database (BDNI), and used to describe different scenarios for the spread of infection within and between herds from a recent outbreak (epidemic) or a five-year-old outbreak (endemic). Results show that rewiring successfully contains infections to a limited number of herds, especially if the outbreak is recent and the estimation of disease prevalence frequent, while the respective impact of the parameters of the algorithm depend on the infection parameters. Allowing any animal movement from high to low-prevalence herds reduces the effectiveness of the algorithm in epidemic settings, while frequent and fine-grained prevalence assessments improve the impact of the algorithm in endemic settings. Our approach focusing on a few commercial movements is expected to lead to substantial improvements in the control of a targeted disease, although changes in the network structure should be monitored for potential vulnerabilities to other diseases. This general algorithm could be applied to any network of controlled individual movements liable to spread disease.","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"1 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vector competence of Culex quinquefasciatus for Tembusu virus and viral factors for virus transmission by mosquitoes","authors":"Yibin Tang, Yu He, Xiaoli Wang, Zhen Wu, Senyan Du, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Xinxin Zhao, Qiao Yang, Ying Wu, Shaqiu Zhang, Juan Huang, Xumin Ou, Di Sun, Anchun Cheng, Shun Chen","doi":"10.1186/s13567-024-01361-3","DOIUrl":"https://doi.org/10.1186/s13567-024-01361-3","url":null,"abstract":"The ongoing epidemic of flaviviruses worldwide has underscored the importance of studying flavivirus vector competence, considering their close association with mosquito vectors. Tembusu virus is an avian-related mosquito-borne flavivirus that has been an epidemic in China and Southeast Asia since 2010. However, the reason for the outbreak of Tembusu virus in 2010 remains unclear, and it is unknown whether changes in vector transmission played an essential role in this process. To address these questions, we conducted a study using Culex quinquefasciatus as a model for Tembusu virus infection, employing both oral infection and microinjection methods. Our findings confirmed that both vertical and venereal transmission collectively contribute to the cycle of Tembusu virus within the mosquito population, with persistent infections observed. Importantly, our data revealed that the prototypical Tembusu virus MM_1775 strain exhibited significantly greater infectivity and transmission rates in mosquitoes than did the duck Tembusu virus (CQW1 strain). Furthermore, we revealed that the viral E protein and 3′ untranslated region are key elements responsible for these differences. In conclusion, our study sheds light on mosquito transmission of Tembusu virus and provides valuable insights into the factors influencing its infectivity and transmission rates. These findings contribute to a better understanding of Tembusu virus epidemiology and can potentially aid in the development of strategies to control its spread.","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"77 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michela Bullone, Alessandro Bellato, Patrizia Robino, Patrizia Nebbia, Sara Morello, Daniela Marchis, Alberto Tarducci, Giuseppe Ru
{"title":"Prevalence and risk factors associated with nasal carriage of methicillin-resistant staphylococci in horses and their caregivers","authors":"Michela Bullone, Alessandro Bellato, Patrizia Robino, Patrizia Nebbia, Sara Morello, Daniela Marchis, Alberto Tarducci, Giuseppe Ru","doi":"10.1186/s13567-024-01364-0","DOIUrl":"https://doi.org/10.1186/s13567-024-01364-0","url":null,"abstract":"Antimicrobial resistance is a global threat, and pet-associated strains may pose a risk to human health. Equine veterinarians are at high risk of carrying methicillin-resistant staphylococci (MRS), but specific risk factors remain elusive, and few data are available for other personnel involved in the horse industry. The prevalence, characteristics, and risk factors for nasal carriage of MRS in horses and their caregivers were studied in northwestern Italy. Nasal swabs from 110 asymptomatic horses housed at 21 barns and 34 human caregivers were collected. Data on barns, horses, and personnel were acquired through questionnaires. The samples were incubated in selective media, and the bacterial isolates were identified by mass spectrometry. Risk factors were investigated by Poisson regression. MRS were isolated from 33 horses (30%), 11 humans (32.4%) and 3 environmental samples (14.2%). Most isolates were multidrug resistant (MDRS). The prevalence of MRS and MDRS was greater in racehorses and their personnel than in pleasurable and jumping/dressing horses. MRS carriage in caregivers was associated with an increased prevalence of MRS carriage in horses. The frequency of antimicrobial treatments administered in the barn during the last 12 months was a risk factor for MRS carriage in horses [prevalence ratio (PR) 3.97, 95% CI 1.11, 14.13] and caregivers (PR 2.00, 95% CI 1.05, 3.82), whereas a good ventilation index of the horse tabling environment was a protective factor (PR 0.43, 95% CI 0.20, 0.92). Our data reveal relevant interactions occurring between bacterial communities of horses and humans that share the same environment, suggesting that One Health surveillance programs should be implemented.","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"20 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The roles and mechanisms of endoplasmic reticulum stress-mediated autophagy in animal viral infections.","authors":"Lan Chen, Miaozhan Wei, Bijun Zhou, Kaigong Wang, Erpeng Zhu, Zhentao Cheng","doi":"10.1186/s13567-024-01360-4","DOIUrl":"10.1186/s13567-024-01360-4","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) is a unique organelle responsible for protein synthesis and processing, lipid synthesis in eukaryotic cells, and the replication of many animal viruses is closely related to ER. A considerable number of viral proteins are synthesised during viral infection, resulting in the accumulation of unfolded and misfolded proteins in ER, which in turn induces endoplasmic reticulum stress (ERS). ERS further drives three signalling pathways (PERK, IRE1, and ATF6) of the cellular unfolded protein response (UPR) to respond to the ERS. In numerous studies, ERS has been shown to mediate autophagy, a highly conserved cellular degradation mechanism to maintain cellular homeostasis in eukaryotic cells, through the UPR to restore ER homeostasis. ERS-mediated autophagy is closely linked to the occurrence and development of numerous viral diseases in animals. Host cells can inhibit viral replication by regulating ERS-mediated autophagy, restoring the ER's normal physiological process. Conversely, many viruses have evolved strategies to exploit ERS-mediated autophagy to achieve immune escape. These strategies include the regulation of PERK-eIF2α-Beclin1, PERK-eIF2α-ATF4-ATG12, IRE1α-JNK-Beclin1, and other signalling pathways, which provide favourable conditions for the replication of animal viruses in host cells. The ERS-mediated autophagy pathway has become a hot topic in animal virological research. This article reviews the most recent research regarding the regulatory functions of ERS-mediated autophagy pathways in animal viral infections, emphasising the underlying mechanisms in the context of different viral infections. Furthermore, it considers the future direction and challenges in the development of ERS-mediated autophagy targeting strategies for combating animal viral diseases, which will contribute to unveiling their pathogenic mechanism from a new perspective and provide a scientific reference for the discovery and development of new antiviral drugs and preventive strategies.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"55 1","pages":"107"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126838","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}
Johann Laubier, Anne Van De Wiele, Aurélie Barboiron, Denis Laloë, Christine Saint-Andrieux, Johan Castille, Emma Meloni, Sonja Ernst, Maryline Pellerin, Sandrine Floriot, Nathalie Daniel-Carlier, Bruno Passet, Joël Merlet, Hélène Verheyden, Vincent Béringue, Olivier Andréoletti, Fiona Houston, Jean-Luc Vilotte, Vincent Bourret, Katayoun Moazami-Goudarzi
{"title":"Variation in the prion protein gene (PRNP) open reading frame sequence in French cervids.","authors":"Johann Laubier, Anne Van De Wiele, Aurélie Barboiron, Denis Laloë, Christine Saint-Andrieux, Johan Castille, Emma Meloni, Sonja Ernst, Maryline Pellerin, Sandrine Floriot, Nathalie Daniel-Carlier, Bruno Passet, Joël Merlet, Hélène Verheyden, Vincent Béringue, Olivier Andréoletti, Fiona Houston, Jean-Luc Vilotte, Vincent Bourret, Katayoun Moazami-Goudarzi","doi":"10.1186/s13567-024-01362-2","DOIUrl":"10.1186/s13567-024-01362-2","url":null,"abstract":"<p><p>The recent emergence of chronic wasting disease (CWD) in Europe has become a new public health risk for monitoring of wild and farmed cervids. This disease, due to prions, has proliferated in North America in a contagious manner. In several mammalian species, polymorphisms in the prion protein gene (PRNP) play a crucial role in the susceptibility to prions and their spread. To obtain a reliable picture of the distribution of PRNP polymorphisms in the two most common cervid species in France, we sequenced the open reading frame (ORF) of this gene in 2114 animals, 1116 roe deer (Capreolus capreolus) and 998 red deer (Cervus elaphus). Selection criteria such as historical origin, spatial distribution and sex ratio have been integrated to establish this sample collection. Except for one heterozygous animal with a non-synonymous mutation at codon 37 (G37A), all the 1116 French roe deer were monomorphic. Red deer showed greater variation with two non-synonymous substitutions (T98A; Q226E), three synonymous substitutions (codons 21, 78 and 136) and a new 24pb deletion (Δ<sub>69-77</sub>). We found significant regional variations between French regions in the frequency of the identified substitutions. After cloning of the PRNP ORF from animals presenting multiple non-synonymous polymorphisms, we identified six haplotypes and obtained a total of twelve genotypes. As in other European countries, we highlighted the apparent homogeneity of PRNP in the French roe deer and the existence of a greater diversity in the red deer. These results were in line with European phylogeographic studies on these two species.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"55 1","pages":"105"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126839","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}
HyeongJin Roh, Kai Ove Skaftnesmo, Dhamotharan Kannimuthu, Abdullah Madhun, Sonal Patel, Bjørn Olav Kvamme, H Craig Morton, Søren Grove
{"title":"Nanopore sequencing provides snapshots of the genetic variation within salmonid alphavirus-3 (SAV3) during an ongoing infection in Atlantic salmon (Salmo salar) and brown trout (Salmo trutta).","authors":"HyeongJin Roh, Kai Ove Skaftnesmo, Dhamotharan Kannimuthu, Abdullah Madhun, Sonal Patel, Bjørn Olav Kvamme, H Craig Morton, Søren Grove","doi":"10.1186/s13567-024-01349-z","DOIUrl":"10.1186/s13567-024-01349-z","url":null,"abstract":"<p><p>Frequent RNA virus mutations raise concerns about evolving virulent variants. The purpose of this study was to investigate genetic variation in salmonid alphavirus-3 (SAV3) over the course of an experimental infection in Atlantic salmon and brown trout. Atlantic salmon and brown trout parr were infected using a cohabitation challenge, and heart samples were collected for analysis of the SAV3 genome at 2-, 4- and 8-weeks post-challenge. PCR was used to amplify eight overlapping amplicons covering 98.8% of the SAV3 genome. The amplicons were subsequently sequenced using the Nanopore platform. Nanopore sequencing identified a multitude of single nucleotide variants (SNVs) and deletions. The variation was widespread across the SAV3 genome in samples from both species. Mostly, specific SNVs were observed in single fish at some sampling time points, but two relatively frequent (i.e., major) SNVs were observed in two out of four fish within the same experimental group. Two other, less frequent (i.e., minor) SNVs only showed an increase in frequency in brown trout. Nanopore reads were de novo clustered using a 99% sequence identity threshold. For each amplicon, a number of variant clusters were observed that were defined by relatively large deletions. Nonmetric multidimensional scaling analysis integrating the cluster data for eight amplicons indicated that late in infection, SAV3 genomes isolated from brown trout had greater variation than those from Atlantic salmon. The sequencing methods and bioinformatics pipeline presented in this study provide an approach to investigate the composition of genetic diversity during viral infections.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"55 1","pages":"106"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126837","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}
Lin Lin, Haixin Bi, Jie Yang, Yuyao Shang, Qingjie Lv, Dajun Zhang, Xi Huang, Mengfei Zhao, Fei Wang, Lin Hua, Huanchun Chen, Bin Wu, Xiangru Wang, Zhong Peng
{"title":"Pasteurella multocida infection induces blood-brain barrier disruption by decreasing tight junctions and adherens junctions between neighbored brain microvascular endothelial cells.","authors":"Lin Lin, Haixin Bi, Jie Yang, Yuyao Shang, Qingjie Lv, Dajun Zhang, Xi Huang, Mengfei Zhao, Fei Wang, Lin Hua, Huanchun Chen, Bin Wu, Xiangru Wang, Zhong Peng","doi":"10.1186/s13567-024-01351-5","DOIUrl":"10.1186/s13567-024-01351-5","url":null,"abstract":"<p><p>Meningitis induced by Pasteurella multocida has been substantially described in clinical practice in both human and veterinary medicine, but the underlying mechanisms have not been previously reported. In this study, we investigated the influence of P. multocida infection on the permeability of the blood-brain barrier (BBB) using different models. Our in vivo tests in a mouse model and in vitro tests using human brain microvascular endothelial cell (hBMEC) model showed that P. multocida infection increased murine BBB permeability in mice and hBMEC monolayer permeability. Furthermore, we observed that P. multocida infection resulted in decreased expression of tight junctions (ZO1, claudin-5, occludin) and adherens junctions (E-cadherin) between neighboring hBMECs. Subsequent experiments revealed that P. multocida infection promoted the activation of hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling and NF-κB signaling, and suppressed the HIF-1α/VEGFA significantly remitted the decrease in ZO1/E-cadherin induced by P. multocida infection (P < 0.001). NF-κB signaling was found to contribute to the production of chemokines such as TNF-1α, IL-β, and IL-6. Additionally, transmission electron microscopy revealed that paracellular migration might be the strategy employed by P. multocida to cross the BBB. This study provides the first evidence of the migration strategy used by P. multocida to traverse the mammalian BBB. The data presented herein will contribute to a better understanding of the pathogenesis of the zoonotic pathogen P. multocida.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"55 1","pages":"104"},"PeriodicalIF":3.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112618","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 hijacks DDX3X protein and induces ferroptosis to facilitate viral replication.","authors":"Qian Mao, Shengming Ma, Shuangyu Li, Yuhua Zhang, Shanshan Li, Wenhui Wang, Fang Wang, Zekun Guo, Chengbao Wang","doi":"10.1186/s13567-024-01358-y","DOIUrl":"10.1186/s13567-024-01358-y","url":null,"abstract":"<p><p>Porcine reproductive and respiratory syndrome virus (PRRSV) is a severe disease with substantial economic consequences for the swine industry. The DEAD-box helicase 3 (DDX3X) is an RNA helicase that plays a crucial role in regulating RNA metabolism, immunological response, and even RNA virus infection. However, it is unclear whether it contributes to PRRSV infection. Recent studies have found that the expression of DDX3X considerably increases in Marc-145 cells when infected with live PRRSV strains Ch-1R and SD16; however, it was observed that inactivated viruses did not lead to any changes. By using the RK-33 inhibitor or DDX3X-specific siRNAs to reduce DDX3X expression, there was a significant decrease in the production of PRRSV progenies. In contrast, the overexpression of DDX3X in host cells substantially increased the proliferation of PRRSV. A combination of transcriptomics and metabolomics investigations revealed that in PRRSV-infected cells, DDX3X gene silencing severely affected biological processes such as ferroptosis, the FoxO signalling pathway, and glutathione metabolism. The subsequent transmission electron microscopy (TEM) imaging displayed the typical ferroptosis features in PRRSV-infected cells, such as mitochondrial shrinkage, reduction or disappearance of mitochondrial cristae, and cytoplasmic membrane rupture. Conversely, the mitochondrial morphology was unchanged in DDX3X-inhibited cells. Furthermore, silencing of the DDX3X gene changed the expression of ferroptosis-related genes and inhibited the virus proliferation, while the drug-induced ferroptosis inversely promoted PRRSV replication. In summary, these results present an updated perspective of how PRRSV infection uses DDX3X for self-replication, potentially leading to ferroptosis via various mechanisms that promote PRRSV replication.</p>","PeriodicalId":23658,"journal":{"name":"Veterinary Research","volume":"55 1","pages":"103"},"PeriodicalIF":3.7,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000777","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}