{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T04:56:11Z","timestamp":1681534571082},"reference-count":70,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural collaborative research grants on Henipaviruses at the Friedrich-Loeffler-Institut","award":["HR-0045","HR-0046"]},{"name":"Federal Excellence Initiative of Mecklenburg Western Pomerania and European Social Fund","award":["ESF\/14-BM-A55-0002\/16"]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respiratory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking in the determination of complex host response patterns in differentiated respiratory tract epithelia for the understanding of NiV replication and spread in swine. Here we characterized infection and spread of NiV in differentiated primary porcine bronchial epithelial cells (PBEC) cultivated at the air\u2013liquid interface (ALI). After the initial infection of only a few apical cells, lateral spread for 12 days with epithelium disruption was observed without releasing substantial amounts of infectious virus from the apical or basal sides. Deep time course proteomics revealed pronounced upregulation of genes related to type I\/II IFN, immunoproteasomal subunits, transporter associated with antigen processing (TAP)-mediated peptide transport, and major histocompatibility complex (MHC) I antigen presentation. Spliceosomal factors were downregulated. We propose a model in which NiV replication in PBEC is slowed by a potent and broad type I\/II IFN host response with conversion from 26S proteasomes to immunoproteasomal antigen processing and improved MHC I presentation for adaptive immunity priming. NiV induced cytopathic effects could reflect the focal release of cell-associated NiV, which may contribute to efficient airborne viral spread between pigs.<\/jats:p>","DOI":"10.3390\/v15040961","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T06:28:12Z","timestamp":1681453692000},"page":"961","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of Nipah Virus Replication and Host Proteome Response Patterns in Differentiated Porcine Airway Epithelial Cells Cultured at the Air\u2013Liquid Interface"],"prefix":"10.3390","volume":"15","author":[{"given":"Martin","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-8707-3442","authenticated-orcid":false,"given":"Kerstin","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany"}]},{"given":"Elisabeth","family":"Woehnke","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-7997-493X","authenticated-orcid":false,"given":"Luca M.","family":"Zaeck","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany"}]},{"given":"Christoph","family":"Pr\u00f6nnecke","sequence":"additional","affiliation":[{"name":"Centre for Biotechnology and Biomedicine, Molecular Biological-Biochemical Processing Technology, Leipzig University, 04103 Leipzig, Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-1603-9861","authenticated-orcid":false,"given":"Michael R.","family":"Knittler","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Greifswald-Insel Riems, Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-0054-7394","authenticated-orcid":false,"given":"Axel","family":"Karger","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-6740-3312","authenticated-orcid":false,"given":"Sandra","family":"Diederich","sequence":"additional","affiliation":[{"name":"Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-8716-2341","authenticated-orcid":false,"given":"Stefan","family":"Finke","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute of Animal Health, 17493 Greifswald-Insel Riems, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S0140-6736(99)04299-3","article-title":"Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia","volume":"354","author":"Chua","year":"1999","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1002\/1531-8249(199909)46:3<428::AID-ANA23>3.0.CO;2-I","article-title":"The neurological manifestations of Nipah virus encephalitis, a novel paramyxovirus","volume":"46","author":"Lee","year":"1999","journal-title":"Ann. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3201\/eid0703.017312","article-title":"Nipah virus infection in bats (order Chiroptera) in peninsular Malaysia","volume":"7","author":"Yob","year":"2001","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9972","DOI":"10.1128\/JVI.74.21.9972-9979.2000","article-title":"The exceptionally large genome of Hendra virus: Support for creation of a new genus within the family Paramyxoviridae","volume":"74","author":"Wang","year":"2000","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3201\/eid1202.051247","article-title":"Nipah virus-associated encephalitis outbreak, Siliguri, India","volume":"12","author":"Chadha","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","first-page":"553","article-title":"Nipah\/Hendra virus outbreak in Siliguri, West Bengal, India in 2001","volume":"123","author":"Harit","year":"2006","journal-title":"Indian J. Med. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1086\/529147","article-title":"Clinical presentation of nipah virus infection in Bangladesh","volume":"46","author":"Hossain","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2010","DOI":"10.1002\/rmv.2010","article-title":"Emerging trends of Nipah virus: A review","volume":"29","author":"Sharma","year":"2019","journal-title":"Rev. Med. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.3201\/eid1110.050513","article-title":"Genetic characterization of Nipah virus, Bangladesh, 2004","volume":"11","author":"Harcourt","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S1286-4579(01)01385-5","article-title":"Comparative pathology of the diseases caused by Hendra and Nipah viruses","volume":"3","author":"Hooper","year":"2001","journal-title":"Microbes Infect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1128\/JVI.02576-12","article-title":"Henipavirus pathogenesis in human respiratory epithelial cells","volume":"87","author":"Escaffre","year":"2013","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1099\/jgv.0.000441","article-title":"Characterization of Nipah virus infection in a model of human airway epithelial cells cultured at an air-liquid interface","volume":"97","author":"Escaffre","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S395","DOI":"10.1093\/infdis\/jiz455","article-title":"Cytokine Induction in Nipah Virus-Infected Primary Human and Porcine Bronchial Epithelial Cells","volume":"221","author":"Elvert","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"F1000 Faculty Rev-1763","DOI":"10.12688\/f1000research.19975.1","article-title":"Recent advances in the understanding of Nipah virus immunopathogenesis and anti-viral approaches","volume":"8","author":"Pelissier","year":"2019","journal-title":"F1000Research"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Leon, A.J., Borisevich, V., Boroumand, N., Seymour, R., Nusbaum, R., Escaffre, O., Xu, L., Kelvin, D.J., and Rockx, B. (2018). Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006343"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e01136-17","DOI":"10.1128\/JVI.01136-17","article-title":"Nipah and Hendra Virus Nucleoproteins Inhibit Nuclear Accumulation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT2 by Interfering with Their Complex Formation","volume":"91","author":"Sugai","year":"2017","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.1128\/JVI.78.10.5358-5367.2004","article-title":"Identification of the nuclear export signal and STAT-binding domains of the Nipah virus V protein reveals mechanisms underlying interferon evasion","volume":"78","author":"Rodriguez","year":"2004","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7828","DOI":"10.1128\/JVI.02610-08","article-title":"Nipah virus sequesters inactive STAT1 in the nucleus via a P gene-encoded mechanism","volume":"83","author":"Ciancanelli","year":"2009","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e01960-17","DOI":"10.1128\/JVI.01960-17","article-title":"Paramyxovirus V Proteins Interact with the RIG-I\/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling","volume":"92","author":"Feinman","year":"2018","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1128\/JVI.02843-12","article-title":"Amino acid requirements for MDA5 and LGP2 recognition by paramyxovirus V proteins: A single arginine distinguishes MDA5 from RIG-I","volume":"87","author":"Rodriguez","year":"2013","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bharaj, P., Wang, Y.E., Dawes, B.E., Yun, T.E., Park, A., Yen, B., Basler, C.F., Freiberg, A.N., Lee, B., and Rajsbaum, R. (2016). The Matrix Protein of Nipah Virus Targets the E3-Ubiquitin Ligase TRIM6 to Inhibit the IKKepsilon Kinase-Mediated Type-I IFN Antiviral Response. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005880"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bojkova, D., Bechtel, M., McLaughlin, K.M., McGreig, J.E., Klann, K., Bellinghausen, C., Rohde, G., Jonigk, D., Braubach, P., and Ciesek, S. (2020). Aprotinin Inhibits SARS-CoV-2 Replication. Cells, 9.","DOI":"10.3390\/cells9112377"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7092","DOI":"10.1038\/s41467-021-27318-0","article-title":"Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2","volume":"12","author":"Hatton","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.molcel.2020.11.028","article-title":"Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2","volume":"80","author":"Hekman","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e105912","DOI":"10.15252\/embj.2020105912","article-title":"An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells","volume":"40","author":"Lamers","year":"2021","journal-title":"EMBO J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e14761","DOI":"10.14814\/phy2.14761","article-title":"SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection","volume":"9","author":"Liou","year":"2021","journal-title":"Physiol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1021\/acs.jproteome.1c00783","article-title":"Deep Time Course Proteomics of SARS-CoV- and SARS-CoV-2-Infected Human Lung Epithelial Cells (Calu-3) Reveals Strong Induction of Interferon-Stimulated Gene Expression by SARS-CoV-2 in Contrast to SARS-CoV","volume":"21","author":"Grossegesse","year":"2022","journal-title":"J. Proteome Res."},{"key":"ref_28","first-page":"183","article-title":"Well-differentiated human airway epithelial cell cultures","volume":"107","author":"Fulcher","year":"2005","journal-title":"Methods. Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7929","DOI":"10.1128\/JVI.00263-06","article-title":"Recombinant nipah virus vaccines protect pigs against challenge","volume":"80","author":"Weingartl","year":"2006","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: Improving support for quantification data","volume":"47","author":"Csordas","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_32","first-page":"329","article-title":"Distribution of the Ratio of the Mean Square Successive Difference to the Variance","volume":"12","year":"1941","journal-title":"Ann. Math. Stat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.coviro.2011.10.008","article-title":"Interferon-stimulated genes and their antiviral effector functions","volume":"1","author":"Schoggins","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/oxfordjournals.jbchem.a124327","article-title":"Interferon-gamma induces different subunit organizations and functional diversity of proteasomes","volume":"115","author":"Aki","year":"1994","journal-title":"J. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1172\/JCI29832","article-title":"Virus-induced type I IFN stimulates generation of immunoproteasomes at the site of infection","volume":"116","author":"Shin","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10230","DOI":"10.1038\/srep10230","article-title":"Regulation of immunoproteasome function in the lung","volume":"5","author":"Keller","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1099\/vir.0.032060-0","article-title":"The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways","volume":"92","author":"Tisoncik","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1074-7613(00)80249-6","article-title":"Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading","volume":"4","author":"Riese","year":"1996","journal-title":"Immunity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"L318","DOI":"10.1152\/ajplung.00174.2003","article-title":"Accessory cell function of airway epithelial cells","volume":"287","author":"Oei","year":"2004","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12931-020-01381-5","article-title":"Cathepsin S: Investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics","volume":"21","author":"Brown","year":"2020","journal-title":"Respir. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.immuni.2004.07.004","article-title":"Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo","volume":"21","author":"Shen","year":"2004","journal-title":"Immunity"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Basha, G., Lizee, G., Reinicke, A.T., Seipp, R.P., Omilusik, K.D., and Jefferies, W.A. (2008). MHC class I endosomal and lysosomal trafficking coincides with exogenous antigen loading in dendritic cells. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003247"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3389\/fimmu.2018.00635","article-title":"The Contribution of Non-Professional Antigen-Presenting Cells to Immunity and Tolerance in the Liver","volume":"9","author":"Mehrfeld","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Amezcua-Guerra, L.M. (2011). Advances in the Etiology, Pathogenesis and Pathology of Vasculitis, InTech.","DOI":"10.5772\/834"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.virol.2010.05.005","article-title":"Characterization of the antiviral and inflammatory responses against Nipah virus in endothelial cells and neurons","volume":"404","author":"Lo","year":"2010","journal-title":"Virology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Cong, Y., Lentz, M.R., Lara, A., Alexander, I., Bartos, C., Bohannon, J.K., Hammoud, D., Huzella, L., Jahrling, P.B., and Janosko, K. (2017). Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005532"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bauer, A., Neumann, S., Karger, A., Henning, A.K., Maisner, A., Lamp, B., Dietzel, E., Kwasnitschka, L., Balkema-Buschmann, A., and Keil, G.M. (2014). ANP32B is a nuclear target of henipavirus M proteins. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097233"},{"key":"ref_48","first-page":"44","article-title":"Interaction of host cellular factor ANP32B with matrix proteins of different paramyxoviruses","volume":"101","author":"Gunther","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, Y.E., Park, A., Lake, M., Pentecost, M., Torres, B., Yun, T.E., Wolf, M.C., Holbrook, M.R., Freiberg, A.N., and Lee, B. (2010). Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001186"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13099","DOI":"10.1128\/JVI.02103-14","article-title":"Matrix proteins of Nipah and Hendra viruses interact with beta subunits of AP-3 complexes","volume":"88","author":"Sun","year":"2014","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1002\/1873-3468.12272","article-title":"Nipah virus matrix protein: Expert hacker of cellular machines","volume":"590","author":"Watkinson","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1038\/s41467-018-05354-7","article-title":"Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response","volume":"9","author":"Rawlinson","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hippee, C.E., Singh, B.K., Thurman, A.L., Cooney, A.L., Pezzulo, A.A., Cattaneo, R., and Sinn, P.L. (2021). Measles virus exits human airway epithelia within dislodged metabolically active infectious centers. PLoS Pathog., 17.","DOI":"10.1101\/2021.03.09.434554"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Alonso, C., Raynor, P.C., Davies, P.R., and Torremorell, M. (2015). Concentration, Size Distribution, and Infectivity of Airborne Particles Carrying Swine Viruses. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135675"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/elps.1150090603","article-title":"Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G-250 and R-250","volume":"9","author":"Neuhoff","year":"1988","journal-title":"Electrophoresis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wisniewski","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1074\/mcp.TIR119.001720","article-title":"MaxQuant Software for Ion Mobility Enhanced Shotgun Proteomics","volume":"19","author":"Prianichnikov","year":"2020","journal-title":"Mol. Cell Proteom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"D635","DOI":"10.1093\/nar\/gkw1104","article-title":"Ensembl 2017","volume":"45","author":"Aken","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_60","unstructured":"R Core Team, R. (2020). A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_61","unstructured":"(2023, March 12). RStudio Team, RStudio: Integrated Development for R. RStudio, PBC, Boston. Available online: http:\/\/www.rstudio.com\/."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_63","unstructured":"Kolberg, L., and Raudvere, U. (2023, March 12). Package \u2018gprofiler2\u2019 Version 0.2.1. Available online: https:\/\/cran.r-project.org\/web\/packages\/gprofiler2\/gprofiler2.pdf."},{"key":"ref_64","unstructured":"Wickham, H.C.W., Takahashi, K., Wilke, C., Woo, K., Yutani, H., and Dunnington, D. (2023, March 12). RStudio Package \u2018ggplot2\u2019\u2014Version 3.3.5. Available online: https:\/\/cran.r-project.org\/web\/packages\/ggplot2\/ggplot2.pdf."},{"key":"ref_65","unstructured":"(2023, March 12). Andri et mult. al. S. DescTools: Tools for Descriptive Statistics. R Package Version 0.99.44. Available online: https:\/\/cran.r-project.org\/package=DescTools."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/961\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T07:22:08Z","timestamp":1681456928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,13]]},"references-count":70,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["v15040961"],"URL":"http:\/\/dx.doi.org\/10.3390\/v15040961","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":["Virology","Infectious Diseases"],"published":{"date-parts":[[2023,4,13]]}}}