{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:11:02Z","timestamp":1783296662844,"version":"3.54.6"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014114","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000}}],"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Strategic Priority Research Program of the Chinese Academy of Sciences","award":["XDB0730100"],"award-info":[{"award-number":["XDB0730100"]}]},{"name":"National Key R&D Plan of the Ministry of Science and Technology, China","award":["2023YFD2400201"],"award-info":[{"award-number":["2023YFD2400201"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The herpesviral haematopoietic necrosis with acute gill hemorrhage has recently become prevalent in gibel carp farming regions and has resulted in significant losses. Although several herpesvirus strains (belonging to\n                    <jats:italic>Cyvirus cyprinidallo2<\/jats:italic>\n                    ) have been isolated, the permissive cells\n                    <jats:italic>in vivo<\/jats:italic>\n                    , how the virus manipulates host cell processes, and causes disease remain largely unclear. In this study, the isolate\n                    <jats:italic>Carassius auratus<\/jats:italic>\n                    herpesvirus (CaHV) was used as a model to dissect the interactions between virus and host through single-cell RNA sequencing (scRNA-seq) and functional validation. Spleen of the infected fish was selected for scRNA-seq analysis for its highest viral load, which resolved splenic cells into ten distinct clusters, and macrophages and mural cells were identified as the major viral permissive cells. By classification of the permissive cells into infected and bystander cells, we found that CaHV induced widespread suppression of host cellular processes in infected cells, especially the antiviral responses. Meanwhile, negative immune regulators and factors potentially involved in viral entry, assembly, and egress, including heparan sulfate and the ESCRT complex, were upregulated to facilitate virus infection. Further sub-clustering and pseudotime inference analysis revealed distinct macrophage subpopulations, while novel subsets emerged with CaHV infection. Macrophage subsets toward M2-like polarization were also observed. In addition, enrichment and apoptosis analyses revealed that the hemorrhagic symptoms in diseased fish resulted from a combination of virus-induced coagulation dysfunction and endothelial cell programmed cell death. Collectively, the present study provides comprehensive new insights into the targeted cells of\n                    <jats:italic>Cyvirus cyprinidallo2<\/jats:italic>\n                    and its interactions with the host, while also identifying potential targets for disease control.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014114","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:33:51Z","timestamp":1775151231000},"page":"e1014114","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell transcriptome profiling reveals herpesviral manipulation of host processes in spleen of gibel carp infected with a Cyvirus cyprinidallo2"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2145-332X","authenticated-orcid":true,"given":"Fei","family":"Ke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Ya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"issue":"1","key":"ppat.1014114.ref001","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s12985-025-02779-7","article-title":"Herpesviruses: overview of systematics, genomic complexity and life cycle","volume":"22","author":"A Dotto-Maurel","year":"2025","journal-title":"Virol J"},{"issue":"4","key":"ppat.1014114.ref002","doi-asserted-by":"crossref","first-page":"100062","DOI":"10.1016\/j.watbs.2022.100062","article-title":"Recent insights into aquatic viruses: Emerging and reemerging pathogens, molecular features, biological effects, and novel investigative approaches","volume":"1","author":"Q-Y Zhang","year":"2022","journal-title":"Water Biology and Security"},{"key":"ppat.1014114.ref003","doi-asserted-by":"crossref","first-page":"001673","DOI":"10.1099\/jgv.0.001673","article-title":"ICTV Virus Taxonomy Profile: Herpesviridae 2021","volume":"102","author":"D Gatherer","year":"2021","journal-title":"J Gen Virol"},{"key":"ppat.1014114.ref004","article-title":"The State of World Fisheries and Aquaculture 2022. Towards Blue Transformation","author":"FAO","year":"2022"},{"issue":"1","key":"ppat.1014114.ref005","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/jam.14616","article-title":"Koi herpesvirus (KHV) and KHV disease (KHVD) - a recently updated overview","volume":"129","author":"SM Bergmann","year":"2020","journal-title":"J Appl Microbiol"},{"issue":"12","key":"ppat.1014114.ref006","doi-asserted-by":"crossref","DOI":"10.1111\/jfd.14016","article-title":"A review of latency in the Alloherpesviridae family","volume":"47","author":"EM Quijano Card\u00e9","year":"2024","journal-title":"J Fish Dis"},{"issue":"5","key":"ppat.1014114.ref007","doi-asserted-by":"crossref","first-page":"658","DOI":"10.3390\/v17050658","article-title":"Genomic and Phenotypic Characterization of a Novel Virulent Strain of Cyvirus cyprinidallo2 Originating from an Outbreak in The Netherlands","volume":"17","author":"B He","year":"2025","journal-title":"Viruses"},{"issue":"3","key":"ppat.1014114.ref008","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1365-2761.1995.tb00296.x","article-title":"Herpesviral haematopoietic necrosis of goldfish, Carassius auratus (L.)","volume":"18","author":"SJ Jung","year":"1995","journal-title":"Journal of Fish Diseases"},{"issue":"9","key":"ppat.1014114.ref009","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/s41559-022-01813-z","article-title":"Comparative genome anatomy reveals evolutionary insights into a unique amphitriploid fish","volume":"6","author":"Y Wang","year":"2022","journal-title":"Nat Ecol Evol"},{"issue":"3","key":"ppat.1014114.ref010","doi-asserted-by":"crossref","first-page":"100271","DOI":"10.1016\/j.watbs.2024.100271","article-title":"Chinese wisdom and modern innovation of aquaculture","volume":"3","author":"J-F Gui","year":"2024","journal-title":"Water Biology and Security"},{"issue":"12","key":"ppat.1014114.ref011","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1007\/s00705-016-3037-y","article-title":"Complete genome sequence and architecture of crucian carp Carassius auratus herpesvirus (CaHV)","volume":"161","author":"X-T Zeng","year":"2016","journal-title":"Arch Virol"},{"issue":"9","key":"ppat.1014114.ref012","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.3390\/v14092068","article-title":"Complete Genome and Molecular Characterization of a New Cyprinid Herpesvirus 2 (CyHV-2) SH-01 Strain Isolated from Cultured Crucian Carp","volume":"14","author":"J Yang","year":"2022","journal-title":"Viruses"},{"issue":"6","key":"ppat.1014114.ref013","doi-asserted-by":"crossref","first-page":"110720","DOI":"10.1016\/j.ygeno.2023.110720","article-title":"Advances on genomes studies of large DNA viruses in aquaculture: A minireview","volume":"115","author":"F Ke","year":"2023","journal-title":"Genomics"},{"key":"ppat.1014114.ref014","first-page":"336","article-title":"Pathological changes of acute viral hemorrhages in the gills of crucian carp","volume":"23","author":"J Fang","year":"2016","journal-title":"J Fishery Sci China"},{"key":"ppat.1014114.ref015","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.vetmic.2013.05.025","article-title":"Cyprinid herpesvirus 2 infection emerged in cultured gibel carp, Carassius auratus gibelio in China","volume":"166","author":"J Xu","year":"2013","journal-title":"Vet Microbiol"},{"issue":"5","key":"ppat.1014114.ref016","article-title":"Proteogenomic analysis of Cyprinid herpesvirus 2 using high-resolution mass spectrometry","volume":"99","author":"C Xu","year":"2025","journal-title":"J Virol"},{"issue":"4","key":"ppat.1014114.ref017","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/s11262-016-1325-y","article-title":"Mutations in the C-terminal region affect subcellular localization of crucian carp herpesvirus (CaHV) GPCR","volume":"52","author":"J Wang","year":"2016","journal-title":"Virus Genes"},{"key":"ppat.1014114.ref018","doi-asserted-by":"crossref","first-page":"109400","DOI":"10.1016\/j.fsi.2024.109400","article-title":"CyHV-2 infection triggers mitochondrial-mediated apoptosis in GiCF cells by upregulating the pro-apoptotic gene ccBAX","volume":"147","author":"W Cheng","year":"2024","journal-title":"Fish Shellfish Immunol"},{"issue":"2","key":"ppat.1014114.ref019","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.fsi.2015.06.011","article-title":"CyHV-2 ORF104 activates the p38 MAPK pathway","volume":"46","author":"M Du","year":"2015","journal-title":"Fish Shellfish Immunol"},{"issue":"1","key":"ppat.1014114.ref020","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1186\/s12864-017-3945-6","article-title":"Distinct herpesvirus resistances and immune responses of three gynogenetic clones of gibel carp revealed by comprehensive transcriptomes","volume":"18","author":"F-X Gao","year":"2017","journal-title":"BMC Genomics"},{"issue":"8","key":"ppat.1014114.ref021","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.3390\/v15081746","article-title":"In Vivo Imaging Sheds Light on the Susceptibility and Permissivity of Carassius auratus to Cyprinid Herpesvirus 2 According to Developmental Stage","volume":"15","author":"B He","year":"2023","journal-title":"Viruses"},{"issue":"3","key":"ppat.1014114.ref022","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.694","article-title":"Single-cell RNA sequencing technologies and applications: A brief overview","volume":"12","author":"D Jovic","year":"2022","journal-title":"Clin Transl Med"},{"issue":"10","key":"ppat.1014114.ref023","article-title":"Single-cell profiling of African swine fever virus disease in the pig spleen reveals viral and host dynamics","volume":"121","author":"Z Zhu","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"ppat.1014114.ref024","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/s41590-020-0762-x","article-title":"Single-cell landscape of immunological responses in patients with COVID-19","volume":"21","author":"J-Y Zhang","year":"2020","journal-title":"Nat Immunol"},{"issue":"6","key":"ppat.1014114.ref025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009665","article-title":"Single-cell RNA-seq landscape midbrain cell responses to red spotted grouper nervous necrosis virus infection","volume":"17","author":"Q Wang","year":"2021","journal-title":"PLoS Pathog"},{"issue":"19","key":"ppat.1014114.ref026","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2201288119","article-title":"Transcriptome profiling in swine macrophages infected with African swine fever virus at single-cell resolution","volume":"119","author":"Y Zheng","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1014114.ref027","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1038\/s41467-023-40148-6","article-title":"Cellular state landscape and herpes simplex virus type 1 infection progression are connected","volume":"14","author":"MK Pietil\u00e4","year":"2023","journal-title":"Nat Commun"},{"key":"ppat.1014114.ref028","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s10499-019-00377-3","article-title":"Protective effect of Clostridium butyricum against Carassius auratus herpesvirus in gibel carp","volume":"27","author":"T Li","year":"2019","journal-title":"Aquacult Int"},{"key":"ppat.1014114.ref029","doi-asserted-by":"crossref","first-page":"109280","DOI":"10.1016\/j.fsi.2023.109280","article-title":"The fish spleen","volume":"144","author":"AG Zapata","year":"2024","journal-title":"Fish Shellfish Immunol"},{"issue":"7","key":"ppat.1014114.ref030","doi-asserted-by":"crossref","first-page":"112793","DOI":"10.1016\/j.celrep.2023.112793","article-title":"Cross-organ single-cell transcriptome profiling reveals macrophage and dendritic cell heterogeneity in zebrafish","volume":"42","author":"Q Zhou","year":"2023","journal-title":"Cell Rep"},{"issue":"3","key":"ppat.1014114.ref031","article-title":"GCRV-II invades monocytes\/macrophages and induces macrophage polarization and apoptosis in tissues to facilitate viral replication and dissemination","volume":"98","author":"N Xia","year":"2024","journal-title":"J Virol"},{"issue":"12","key":"ppat.1014114.ref032","doi-asserted-by":"crossref","first-page":"7573","DOI":"10.4049\/jimmunol.1002401","article-title":"Characterization of fish IRF3 as an IFN-inducible protein reveals evolving regulation of IFN response in vertebrates","volume":"185","author":"F Sun","year":"2010","journal-title":"J Immunol"},{"issue":"8","key":"ppat.1014114.ref033","doi-asserted-by":"crossref","first-page":"104821","DOI":"10.1016\/j.isci.2022.104821","article-title":"LGP2 is essential for zebrafish survival through dual regulation of IFN antiviral response","volume":"25","author":"X-Y Gong","year":"2022","journal-title":"iScience"},{"issue":"4","key":"ppat.1014114.ref034","article-title":"Identification of a novel Gig2 gene family specific to non-amniote vertebrates","volume":"8","author":"Y-B Zhang","year":"2013","journal-title":"PLoS One"},{"issue":"14","key":"ppat.1014114.ref035","doi-asserted-by":"crossref","first-page":"4818","DOI":"10.3390\/ijms21144818","article-title":"ASGR1 and Its Enigmatic Relative, CLEC10A","volume":"21","author":"JK Hoober","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"4","key":"ppat.1014114.ref036","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1002\/JLB.3VMR0118-036R","article-title":"Galectin-3-binding protein: A multitask glycoprotein with innate immunity functions in viral and bacterial infections","volume":"104","author":"V Loimaranta","year":"2018","journal-title":"J Leukoc Biol"},{"issue":"5","key":"ppat.1014114.ref037","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1161\/ATVBAHA.113.303153","article-title":"Macrophage inflammatory markers are associated with subclinical carotid artery disease in women with human immunodeficiency virus or hepatitis C virus infection","volume":"34","author":"I Shaked","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ppat.1014114.ref038","article-title":"Macrophage expressed TRIM47 is required to control RNA virus infection by targeting MAVS","volume":"212","author":"W Lu","year":"2024","journal-title":"The Journal of Immunology"},{"key":"ppat.1014114.ref039","doi-asserted-by":"crossref","first-page":"124027","DOI":"10.1016\/j.ijbiomac.2023.124027","article-title":"Intelectin enhances the phagocytosis of macrophages via CDC42-WASF2-ARPC2 signaling axis in Megalobrama amblycephala","volume":"236","author":"H Cui","year":"2023","journal-title":"Int J Biol Macromol"},{"issue":"6","key":"ppat.1014114.ref040","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.121.024424","article-title":"Haptoglobin Regulates Macrophage\/Microglia-Induced Inflammation and Prevents Ischemic Brain Damage Via Binding to HMGB1","volume":"11","author":"M Morimoto","year":"2022","journal-title":"J Am Heart Assoc"},{"key":"ppat.1014114.ref041","doi-asserted-by":"crossref","DOI":"10.1007\/978-981-99-5340-0_7","article-title":"Role of vitellogenin as immunocompetent molecule","volume-title":"Vitellogenin in fishes- diversification, biological properties, and future perspectives","author":"SP Shoba","year":"2023"},{"key":"ppat.1014114.ref042","doi-asserted-by":"crossref","first-page":"803244","DOI":"10.3389\/fimmu.2021.803244","article-title":"Alpha-2-macroglobulin in inflammation, immunity and infections","volume":"12","author":"J Vandooren","year":"2021","journal-title":"Front Immunol"},{"issue":"1","key":"ppat.1014114.ref043","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1038\/s41467-022-30879-3","article-title":"Leukocyte cell-derived chemotaxin 2 is an antiviral regulator acting through the proto-oncogene MET","volume":"13","author":"T Shirasaki","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"ppat.1014114.ref044","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/s42003-022-03911-x","article-title":"TOB1 attenuates IRF3-directed antiviral responses by recruiting HDAC8 to specifically suppress IFN-\u03b2 expression","volume":"5","author":"Z Yu","year":"2022","journal-title":"Commun Biol"},{"key":"ppat.1014114.ref045","doi-asserted-by":"crossref","first-page":"140088","DOI":"10.1016\/j.ijbiomac.2025.140088","article-title":"A comprehensive review of GPR84: A novel player in pathophysiology and treatment","volume":"300","author":"T Bai","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"ppat.1014114.ref046","doi-asserted-by":"crossref","first-page":"101772","DOI":"10.1016\/j.genrep.2023.101772","article-title":"CD59: Biological function and its potential for drug target action","volume":"31","author":"RM Sarmoko","year":"2023","journal-title":"Gene Reports"},{"issue":"6","key":"ppat.1014114.ref047","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.biochi.2011.03.001","article-title":"Structural and biological characterization of Nattectin, a new C-type lectin from the venomous fish Thalassophryne nattereri","volume":"93","author":"M Lopes-Ferreira","year":"2011","journal-title":"Biochimie"},{"issue":"5","key":"ppat.1014114.ref048","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1161\/CIRCULATIONAHA.122.059062","article-title":"Macrophage-Derived 25-Hydroxycholesterol Promotes Vascular Inflammation, Atherogenesis, and Lesion Remodeling","volume":"147","author":"A Canfr\u00e1n-Duque","year":"2023","journal-title":"Circulation"},{"issue":"7926","key":"ppat.1014114.ref049","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41586-022-05111-3","article-title":"LACC1 bridges NOS2 and polyamine metabolism in inflammatory macrophages","volume":"609","author":"Z Wei","year":"2022","journal-title":"Nature"},{"issue":"1","key":"ppat.1014114.ref050","doi-asserted-by":"crossref","first-page":"5884","DOI":"10.1038\/s41467-024-50212-4","article-title":"An extended interaction site determines binding between AP180 and AP2 in clathrin mediated endocytosis","volume":"15","author":"S Naudi-Fabra","year":"2024","journal-title":"Nat Commun"},{"issue":"5","key":"ppat.1014114.ref051","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/biolre\/ioad100","article-title":"Pro-inflammatory cytokine IL1\u03b21 participates in promoting parturition related pathways in the ovoviviparous teleost black rockfish (Sebastes schlegelii)","volume":"109","author":"S Yan","year":"2023","journal-title":"Biol Reprod"},{"issue":"13","key":"ppat.1014114.ref052","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.120.016615","article-title":"AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP-Dependent Signaling Pathways in the Heart and Various Signaling Systems","volume":"9","author":"H Qasim","year":"2020","journal-title":"J Am Heart Assoc"},{"issue":"18","key":"ppat.1014114.ref053","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2320609121","article-title":"The scaffolding protein AKAP12 regulates mRNA localization and translation","volume":"121","author":"MR Smith","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"ppat.1014114.ref054","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.trecan.2022.02.006","article-title":"C1q+ macrophages: passengers or drivers of cancer progression","volume":"8","author":"M Revel","year":"2022","journal-title":"Trends Cancer"},{"issue":"2","key":"ppat.1014114.ref055","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s12026-022-09330-8","article-title":"Macrophage subsets and their role: co-relation with colony-stimulating factor-1 receptor and clinical relevance","volume":"71","author":"S Yadav","year":"2023","journal-title":"Immunol Res"},{"issue":"8","key":"ppat.1014114.ref056","article-title":"ApoE expression in macrophages communicates immunometabolic signaling that controls hyperlipidemia-driven hematopoiesis & inflammation via extracellular vesicles","volume":"12","author":"TA Phu","year":"2023","journal-title":"J Extracell Vesicles"},{"issue":"1","key":"ppat.1014114.ref057","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1186\/s12885-024-12105-z","article-title":"APOC1 is a prognostic biomarker associated with M2 macrophages in ovarian cancer","volume":"24","author":"S Yang","year":"2024","journal-title":"BMC Cancer"},{"key":"ppat.1014114.ref058","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cca.2020.02.025","article-title":"Endogenous ApoA-I expression in macrophages: A potential target for protection against atherosclerosis","volume":"505","author":"W Chen","year":"2020","journal-title":"Clin Chim Acta"},{"issue":"1","key":"ppat.1014114.ref059","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s10020-024-00805-y","article-title":"Omentin-1 inhibits the development of benign prostatic hyperplasia by attenuating local inflammation","volume":"30","author":"Y-Y Wang","year":"2024","journal-title":"Mol Med"},{"key":"ppat.1014114.ref060","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.molimm.2019.01.017","article-title":"Circulating CD14+CD163+CD209+ M2-like monocytes are associated with the severity of infection in Helicobacter pylori-positive patients","volume":"108","author":"J Hou","year":"2019","journal-title":"Mol Immunol"},{"issue":"4","key":"ppat.1014114.ref061","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1007\/s11427-024-2698-6","article-title":"BEND6 promotes RNA viruses\u2019 replication by inhibiting innate immune responses","volume":"68","author":"T Chen","year":"2025","journal-title":"Sci China Life Sci"},{"issue":"2","key":"ppat.1014114.ref062","doi-asserted-by":"crossref","first-page":"840","DOI":"10.3390\/ijms26020840","article-title":"NLRC3 Attenuates Antiviral Innate Immune Response by Targeting IRF7 in Grass Carp (Ctenopharyngodon idelus)","volume":"26","author":"L Zhang","year":"2025","journal-title":"Int J Mol Sci"},{"key":"ppat.1014114.ref063","doi-asserted-by":"crossref","first-page":"778752","DOI":"10.3389\/fonc.2021.778752","article-title":"Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression","volume":"11","author":"C Marques","year":"2021","journal-title":"Front Oncol"},{"issue":"7","key":"ppat.1014114.ref064","doi-asserted-by":"crossref","first-page":"593","DOI":"10.3390\/v11070593","article-title":"Ranaviruses Bind Cells from Different Species through Interaction with Heparan Sulfate","volume":"11","author":"F Ke","year":"2019","journal-title":"Viruses"},{"key":"ppat.1014114.ref065","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s11046-015-9979-x","article-title":"The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ","volume":"181","author":"Y Zhang","year":"2016","journal-title":"Mycopathologia"},{"issue":"6","key":"ppat.1014114.ref066","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.00979-25","article-title":"\u03b2-Coronaviruses exploit ESCRT for virion assembly and egress","volume":"16","author":"Y Zhang","year":"2025","journal-title":"mBio"},{"issue":"1","key":"ppat.1014114.ref067","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00251-020-01196-0","article-title":"Anatomy of teleost fish immune structures and organs","volume":"73","author":"H Bj\u00f8rgen","year":"2021","journal-title":"Immunogenetics"},{"issue":"6","key":"ppat.1014114.ref068","article-title":"Single-cell transcriptome profiling reveals diverse immune cell populations and their responses to viral infection in the spleen of zebrafish","volume":"37","author":"C-B Hu","year":"2023","journal-title":"FASEB J"},{"issue":"9","key":"ppat.1014114.ref069","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1007\/s11427-022-2293-4","article-title":"FishSCT: a zebrafish-centric database for exploration and visualization of fish single-cell transcriptome","volume":"66","author":"C Guo","year":"2023","journal-title":"Sci China Life Sci"},{"issue":"1","key":"ppat.1014114.ref070","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41467-024-45029-0","article-title":"Cebp1 and Cebp\u03b2 transcriptional axis controls eosinophilopoiesis in zebrafish","volume":"15","author":"G Li","year":"2024","journal-title":"Nat Commun"},{"key":"ppat.1014114.ref071","doi-asserted-by":"crossref","first-page":"1521269","DOI":"10.3389\/fgene.2024.1521269","article-title":"Integrating single-cell RNA-seq and bulk RNA-seq to explore prognostic value and immune landscapes of methionine metabolism-related signature in breast cancer","volume":"15","author":"Y Gao","year":"2025","journal-title":"Front Genet"},{"issue":"5","key":"ppat.1014114.ref072","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.3390\/ijms26052107","article-title":"The Multifaceted Role of Macrophages in Biology and Diseases","volume":"26","author":"J Brancewicz","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"12","key":"ppat.1014114.ref073","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1128\/JVI.03678-13","article-title":"Epstein-Barr virus infection induces indoleamine 2,3-dioxygenase expression in human monocyte-derived macrophages through p38\/mitogen-activated protein kinase and NF-\u03baB pathways: impairment in T cell functions","volume":"88","author":"W Liu","year":"2014","journal-title":"J Virol"},{"issue":"3","key":"ppat.1014114.ref074","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01887-18","article-title":"Infection and Functional Modulation of Human Monocytes and Macrophages by Varicella-Zoster Virus","volume":"93","author":"JJ Kennedy","year":"2019","journal-title":"J Virol"},{"issue":"2","key":"ppat.1014114.ref075","article-title":"Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity","volume":"8","author":"R Blecher-Gonen","year":"2019","journal-title":"Cell Syst"},{"issue":"7","key":"ppat.1014114.ref076","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.05.006","article-title":"Host-Viral Infection Maps Reveal Signatures of Severe COVID-19 Patients","volume":"181","author":"P Bost","year":"2020","journal-title":"Cell"},{"key":"ppat.1014114.ref077","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3390\/v15010226","article-title":"HSV replication: triggering and repressing STING functionality","volume":"15","author":"E Krawczyk","year":"2023","journal-title":"Viruses"},{"issue":"5","key":"ppat.1014114.ref078","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.it.2025.03.007","article-title":"Epstein-Barr virus-mediated immune evasion in tumor promotion","volume":"46","author":"L Yuan","year":"2025","journal-title":"Trends Immunol"},{"key":"ppat.1014114.ref079","doi-asserted-by":"crossref","first-page":"110372","DOI":"10.1016\/j.fsi.2025.110372","article-title":"Cyprinid herpesvirus 2 (CyHV-2) ORF67 inhibits IFN expression by competitively obstructing STING phosphorylation","volume":"163","author":"B-J Cui","year":"2025","journal-title":"Fish Shellfish Immunol"},{"key":"ppat.1014114.ref080","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/978-3-030-34521-1_32","article-title":"Heparanase, Heparan Sulfate and Viral Infection","volume":"1221","author":"A Agelidis","year":"2020","journal-title":"Adv Exp Med Biol"},{"issue":"7","key":"ppat.1014114.ref081","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1013341","article-title":"Identification of the human cytomegalovirus gHgLgO trimer as the central player in virion infectivity","volume":"21","author":"L Thiessen","year":"2025","journal-title":"PLoS Pathog"},{"key":"ppat.1014114.ref082","doi-asserted-by":"crossref","first-page":"105786","DOI":"10.1016\/j.antiviral.2023.105786","article-title":"ESCRT machinery and virus infection","volume":"221","author":"J Dai","year":"2024","journal-title":"Antiviral Res"},{"issue":"4","key":"ppat.1014114.ref083","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s12276-024-01207-0","article-title":"Viral remodeling of the 4D nucleome","volume":"56","author":"K-D Kim","year":"2024","journal-title":"Exp Mol Med"},{"issue":"1","key":"ppat.1014114.ref084","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/s12864-017-3824-1","article-title":"Differences in responses of grass carp to different types of grass carp reovirus (GCRV) and the mechanism of hemorrhage revealed by transcriptome sequencing","volume":"18","author":"L He","year":"2017","journal-title":"BMC Genomics"},{"issue":"2","key":"ppat.1014114.ref085","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1089\/zeb.2019.1843","article-title":"Proteomic Profiling of Zebrafish Challenged by Spring Viremia of Carp Virus Provides Insight into Skin Antiviral Response","volume":"17","author":"R Liu","year":"2020","journal-title":"Zebrafish"},{"key":"ppat.1014114.ref086","doi-asserted-by":"crossref","first-page":"1040093","DOI":"10.3389\/fmicb.2022.1040093","article-title":"Hemorrhagic fever viruses: Pathogenesis, therapeutics, and emerging and re-emerging potential","volume":"13","author":"L Fl\u00f3rez-\u00c1lvarez","year":"2022","journal-title":"Front Microbiol"},{"issue":"2","key":"ppat.1014114.ref087","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.watbs.2024.100253","article-title":"A novel cell line established from skin tissue of gibel carp (Carassius gibelio) is susceptible to Carassius auratus herpesvirus infection","volume":"3","author":"Q-Q Jiang","year":"2024","journal-title":"Water Biology and Security"},{"issue":"43","key":"ppat.1014114.ref088","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1014114.ref089","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13578-021-00742-x","article-title":"Replication and transcription machinery for ranaviruses: components, correlation, and functional architecture","volume":"12","author":"F Ke","year":"2022","journal-title":"Cell Biosci"},{"key":"ppat.1014114.ref090","doi-asserted-by":"crossref","first-page":"140979","DOI":"10.1016\/j.ijbiomac.2025.140979","article-title":"Extra peptidase of a cyanophage confers its stronger lytic effect on bloom-forming Microcystis aeruginosa","volume":"304","author":"F Ke","year":"2025","journal-title":"Int J Biol Macromol"},{"issue":"1","key":"ppat.1014114.ref091","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ymeth.2014.08.016","article-title":"Multiplexed immunohistochemistry, imaging, and quantitation: a review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis","volume":"70","author":"EC Stack","year":"2014","journal-title":"Methods"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1014114","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T17:56:44Z","timestamp":1775671004000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014114"}},"subtitle":[],"editor":[{"given":"Pinghui","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":91,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014114","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]}}}