{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:51:45Z","timestamp":1790023905166,"version":"4.0.1"},"reference-count":99,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T00:00:00Z","timestamp":1537315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The rabbit caliciviruses Lagovirus europaeus GI.1 and GI.2 both cause acute necrotizing hepatitis in European rabbits (Oryctolagus cuniculus). Whilst GI.2 is highly virulent in both young and adult rabbits, rabbits younger than eight weeks of age are highly resistant to disease caused by GI.1, although they are still permissive to infection and viral replication. To investigate the underlying mechanism(s) of this age related resistance to GI.1, we compared liver transcriptomes of young rabbits infected with GI.1 to those of adult rabbits infected with GI.1 and young rabbits infected with GI.2. Our data suggest that kittens have constitutively heightened innate immune responses compared to adult rabbits, particularly associated with increased expression of major histocompatibility class II molecules and activity of natural killer cells, macrophages, and cholangiocytes. This enables them to respond more rapidly to GI.1 infection than adult rabbits and thus limit virus-induced pathology. In contrast, these responses were not fully developed during GI.2 infection. We speculate that the observed downregulation of multiple genes associated with innate immunity in kittens during GI.2 infection may be due to virally-mediated immunomodulation, permitting fatal disease to develop. Our study provides insight into the fundamental host\u2013pathogen interactions responsible for the differences in age-related susceptibility, which likely plays a critical role in defining the success of GI.2 in outcompeting GI.1 in the field.<\/jats:p>","DOI":"10.3390\/v10090512","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T10:50:31Z","timestamp":1537354231000},"page":"512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Robust Innate Immunity of Young Rabbits Mediates Resistance to Rabbit Hemorrhagic Disease Caused by Lagovirus Europaeus GI.1 But Not GI.2"],"prefix":"10.3390","volume":"10","author":[{"given":"Matthew J.","family":"Neave","sequence":"first","affiliation":[{"name":"CSIRO Australian Animal Health Laboratory, Geelong, VIC 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-2990","authenticated-orcid":false,"given":"Robyn N.","family":"Hall","sequence":"additional","affiliation":[{"name":"CSIRO Health and Biosecurity, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Huang","sequence":"additional","affiliation":[{"name":"CSIRO Health and Biosecurity, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth A.","family":"McColl","sequence":"additional","affiliation":[{"name":"CSIRO Australian Animal Health Laboratory, Geelong, VIC 3220, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kerr","sequence":"additional","affiliation":[{"name":"CSIRO Health and Biosecurity, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Hoehn","sequence":"additional","affiliation":[{"name":"CSIRO Health and Biosecurity, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Taylor","sequence":"additional","affiliation":[{"name":"CSIRO Agriculture and Food, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Strive","sequence":"additional","affiliation":[{"name":"CSIRO Health and Biosecurity, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1297-9716-43-12","article-title":"Rabbit haemorrhagic disease (RHD) and rabbit haemorrhagic disease virus (RHDV): A review","volume":"43","author":"Abrantes","year":"2012","journal-title":"Vet. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1136\/vr.d697","article-title":"Detection of a new variant of rabbit haemorrhagic disease virus in France","volume":"168","author":"Zwingelstein","year":"2011","journal-title":"Vet. Rec."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1099\/jgv.0.000840","article-title":"Proposal for a unified classification system and nomenclature of lagoviruses","volume":"98","author":"Abrantes","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1071\/WR02010","article-title":"Rabbit haemorrhagic disease and the biological control of wild rabbits, Oryctolagus cuniculus, in Australia and New Zealand","volume":"29","author":"Cooke","year":"2002","journal-title":"Wildl. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.3201\/eid1812.120341","article-title":"Variant rabbit hemorrhagic disease virus in young rabbits, Spain","volume":"18","author":"Dalton","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.3201\/eid1911.130908","article-title":"New variant of rabbit hemorrhagic disease virus, Portugal, 2012\u20132013","volume":"19","author":"Abrantes","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1136\/vr.g2345","article-title":"Incursion of RHDV2-like variant in Great Britain","volume":"174","author":"Westcott","year":"2014","journal-title":"Vet. Rec."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1136\/vr.g2781","article-title":"RHDV variant 2 presence detected in Scotland","volume":"174","author":"Baily","year":"2014","journal-title":"Vet. Rec."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.meegid.2015.08.005","article-title":"Rabbit haemorrhagic disease virus 2 (RHDV2) outbreak in Azores: Disclosure of common genetic markers and phylogenetic segregation within the European strains","volume":"35","author":"Duarte","year":"2015","journal-title":"Infect. Genet. Evol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.meegid.2016.06.034","article-title":"Emerging rabbit haemorrhagic disease virus 2 (RHDV2) at the gates of the African continent","volume":"44","author":"Valladares","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1136\/vr.i5530","article-title":"RHDV-2 on the Isle of Man and in the Republic of Ireland","volume":"179","author":"Rocchi","year":"2016","journal-title":"Vet. Rec."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/tbed.12650","article-title":"Arrival of rabbit haemorrhagic disease virus 2 to northern Europe: Emergence and outbreaks in wild and domestic rabbits (Oryctolagus cuniculus) in Sweden","volume":"65","author":"Neimanis","year":"2017","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.3201\/eid2112.151210","article-title":"Emerging rabbit hemorrhagic disease virus 2 (RHDVb), Australia","volume":"21","author":"Hall","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3390\/v7010027","article-title":"Is the new variant RHDV replacing genogroup 1 in Portuguese wild rabbit populations?","volume":"7","author":"Lopes","year":"2014","journal-title":"Viruses"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mahar, J.E., Hall, R.N., Peacock, D., Kovaliski, J., Piper, M., Mourant, R., Huang, N., Campbell, S., Gu, X., and Read, A. (2017). Rabbit haemorrhagic disease virus 2 (GI.2) is replacing endemic strains of RHDV in the Australian landscape within 18 months of its arrival. J. Virol., 92.","DOI":"10.1128\/JVI.01374-17"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/1297-9716-44-81","article-title":"Emergence of a new lagovirus related to rabbit haemorrhagic disease virus","volume":"44","author":"Lavazza","year":"2013","journal-title":"Vet. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1297-9716-44-96","article-title":"The new French 2010 rabbit hemorrhagic disease virus causes an RHD-like disease in the Sardinian Cape hare (Lepus capensis mediterraneus)","volume":"44","author":"Puggioni","year":"2013","journal-title":"Vet. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.rvsc.2014.10.008","article-title":"Detection of the new emerging rabbit haemorrhagic disease type 2 virus (RHDV2) in Sicily from rabbit (Oryctolagus cuniculus) and Italian hare (Lepus corsicanus)","volume":"97","author":"Camarda","year":"2014","journal-title":"Res. Vet. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1111\/tbed.12562","article-title":"Spillover events of infection of brown hares (Lepus europaeus) with rabbit haemorrhagic disease type 2 virus (RHDV2) caused sporadic cases of an European brown hare syndrome-like disease in Italy and Spain","volume":"64","author":"Velarde","year":"2016","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1136\/vr.104034","article-title":"Detection of RHDV2 in European brown hares (Lepus europaeus) in Australia","volume":"180","author":"Hall","year":"2016","journal-title":"Vet. Rec."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1099\/vir.0.000070","article-title":"Full genomic analysis of new variant rabbit hemorrhagic disease virus revealed multiple recombination events","volume":"96","author":"Lopes","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_22","first-page":"e444","article-title":"A strain-specific multiplex RT-PCR for Australian rabbit haemorrhagic disease viruses uncovers a new recombinant virus variant in rabbits and hares","volume":"65","author":"Hall","year":"2017","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"269","DOI":"10.20506\/rst.10.2.549","article-title":"Hepatitis of viral origin in Leporidae: Introduction and aetiological hypotheses","volume":"10","author":"Morisse","year":"1991","journal-title":"Rev. Sci. Tech."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1071\/WR99074","article-title":"Effect of inoculation route and ambient temperature on the survival time of rabbits, Oryctolagus cuniculus, infected with Rabbit Haemorrhagic Disease Virus","volume":"27","author":"Cooke","year":"2000","journal-title":"Wildl. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1136\/vr.104132","article-title":"Increased pathogenicity in rabbit haemorrhagic disease virus type 2 (RHDV2)","volume":"180","author":"Capucci","year":"2017","journal-title":"Vet. Rec."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1099\/jgv.0.000355","article-title":"Identification of novel rabbit hemorrhagic disease virus B-cell epitopes and their interaction with host histo-blood group antigens","volume":"97","author":"Song","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1128\/JVI.02832-14","article-title":"Structural analysis of a rabbit hemorrhagic disease virus binding to histo-blood group antigens","volume":"89","author":"Leuthold","year":"2015","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nystrom, K., Le Gall-Recule, G., Grassi, P., Abrantes, J., Ruvoen-Clouet, N., Le Moullac-Vaidye, B., Lopes, A.M., Esteves, P.J., Strive, T., and Marchandeau, S. (2011). Histo-blood group antigens act as attachment factors of rabbit hemorrhagic disease virus infection in a virus strain-dependent manner. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002188"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/glycob\/cwn098","article-title":"Association between expression of the H histo-blood group antigen, alpha1,2fucosyltransferases polymorphism of wild rabbits, and sensitivity to rabbit hemorrhagic disease virus","volume":"19","author":"Guillon","year":"2009","journal-title":"Glycobiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11950","DOI":"10.1128\/JVI.74.24.11950-11954.2000","article-title":"Binding of rabbit hemorrhagic disease virus to antigens of the ABH histo-blood group family","volume":"74","author":"Ganiere","year":"2000","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lopes, A.M., Breiman, A., Lora, M., Le Moullac-Vaidye, B., Galanina, O., Nystr\u00f6m, K., Marchandeau, S., Le Gall-Recul\u00e9, G., Strive, T., and Neimanis, A. (2017). Host specific glycans are correlated with susceptibility to infection by lagoviruses, but not with their virulence. J. Virol., 92.","DOI":"10.1128\/JVI.01759-17"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1053\/jcpa.2000.0403","article-title":"Apoptosis in rabbit haemorrhagic disease","volume":"123","author":"Jung","year":"2000","journal-title":"J. Comp. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1053\/rvsc.1999.0357","article-title":"Immunohistochemical localisation of rabbit haemorrhagic disease virus VP-60 antigen in early infection of young and adult rabbits","volume":"68","author":"Prieto","year":"2000","journal-title":"Res. Vet. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"371","DOI":"10.20506\/rst.10.2.560","article-title":"Clinical and pathological features of viral haemorrhagic disease of rabbits and the European brown hare syndrome","volume":"10","author":"Marcato","year":"1991","journal-title":"Rev. Sci. Tech."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/BF01309598","article-title":"Immunohistochemical localization of the rabbit haemorrhagic disease viral antigen","volume":"127","author":"Alexandrov","year":"1992","journal-title":"Arch. Virol."},{"key":"ref_36","first-page":"237","article-title":"Immunohistological diagnosis of rabbit haemorrhagic disease (RHD)","volume":"39","author":"Ackermann","year":"1992","journal-title":"Zbl. Veterinarmed. B"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0034-5288(92)90028-Z","article-title":"Detection of rabbit haemorrhagic disease virus antigen in tissues by immunohistochemistry","volume":"52","author":"Park","year":"1992","journal-title":"Res. Vet. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0168-1702(98)00144-0","article-title":"Macrophage tropism of rabbit hemorrhagic disease virus is associated with vascular pathology","volume":"60","author":"Parra","year":"1999","journal-title":"Virus Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0166-0934(98)00030-5","article-title":"Detection of rabbit haemorrhagic disease virus (RHDV) by in situ hybridisation with a digoxigenin labelled RNA probe","volume":"72","author":"Gelmetti","year":"1998","journal-title":"J. Virol. Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0021-9975(92)90100-9","article-title":"Comparative histopathological study of rabbit haemorrhagic disease (RHD) and European brown hare syndrome (EBHS)","volume":"107","author":"Fuchs","year":"1992","journal-title":"J. Comp. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.rvsc.2003.08.003","article-title":"Transient decrease in blood heterophils and sustained liver damage caused by calicivirus infection of young rabbits that are naturally resistant to rabbit haemorrhagic disease","volume":"76","author":"Ferreira","year":"2004","journal-title":"Res. Vet. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s11259-006-3297-1","article-title":"Liver enzymes and ultrastructure in rabbit haemorrhagic disease (RHD)","volume":"30","author":"Ferreira","year":"2006","journal-title":"Vet. Res. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1067\/mlc.2003.30","article-title":"Rabbit hemorrhagic viral disease: Characterization of a new animal model of fulminant liver failure","volume":"141","author":"Tunon","year":"2003","journal-title":"J. Lab. Clin. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.rvsc.2005.05.007","article-title":"Severe leukopenia and liver biochemistry changes in adult rabbits after calicivirus infection","volume":"80","author":"Ferreira","year":"2006","journal-title":"Res. Vet. Sci."},{"key":"ref_45","first-page":"443","article-title":"Hematological parameters and visceral lesions relationships in rabbit viral hemorrhagic disease","volume":"39","author":"Plassiart","year":"1992","journal-title":"Zbl. Veterinarmed. B"},{"key":"ref_46","first-page":"133","article-title":"Disseminated intravascular coagulation (DIC) in rabbit haemorrhagic disease","volume":"40","author":"Ueda","year":"1992","journal-title":"Jpn. J. Vet. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1071\/WR00119","article-title":"Statistical models for the effect of age and maternal antibodies on the development of rabbit haemorrhagic disease in Australian wild rabbits","volume":"29","author":"Robinson","year":"2002","journal-title":"Wildl. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.vetimm.2007.09.005","article-title":"Adult rabbits acquire resistance to lethal calicivirus infection by adoptive transfer of sera from infected young rabbits","volume":"121","author":"Ferreira","year":"2008","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/1743-422X-11-109","article-title":"Comparative quantitative monitoring of rabbit haemorrhagic disease viruses in rabbit kittens","volume":"11","author":"Matthaei","year":"2014","journal-title":"Virol. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1053\/rvsc.1998.0266","article-title":"Hepatic lesions in young rabbits experimentally infected with rabbit haemorrhagic disease virus","volume":"66","author":"Mikami","year":"1999","journal-title":"Res. Vet. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.vetimm.2012.09.038","article-title":"Early inflammatory response of young rabbits attending natural resistance to calicivirus (RHDV) infection","volume":"150","author":"Marques","year":"2012","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1297-9716-45-14","article-title":"Immunosuppression abrogates resistance of young rabbits to rabbit haemorrhagic disease (RHD)","volume":"45","author":"Marques","year":"2014","journal-title":"Vet. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0923-2516(96)80587-5","article-title":"Partial characterization of the human erythrocyte receptor for rabbit haemorrhagic disease virus","volume":"146","author":"Blanchard","year":"1995","journal-title":"Res. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.vetmic.2012.01.018","article-title":"Serological assays to discriminate rabbit haemorrhagic disease virus from Australian non-pathogenic rabbit calicivirus","volume":"157","author":"Liu","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13567-018-0540-z","article-title":"Elucidation of the pathology and tissue distribution of Lagovirus europaeus GI.2\/RHDV2 (rabbit haemorrhagic disease virus 2) in young and adult rabbits (Oryctolagus cuniculus)","volume":"49","author":"Neimanis","year":"2018","journal-title":"Vet. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: Tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_61","unstructured":"Alexa, A., and Rahnenfuhrer, J. (2010, October 01). topGO: Enrichment Analysis for Gene Ontology. Bioconductor. Available online: http:\/\/www.bioconductor.org\/packages\/\/2.10\/bioc\/html\/topGO.html."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ritchie, M.E., Phipson, B., Wu, D., Hu, Y., Law, C.W., Shi, W., and Smyth, G.K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res., 43.","DOI":"10.1093\/nar\/gkv007"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2009). ggplot2: Elegant Graphics for Data Analysis, Springer Publishing Company.","DOI":"10.1007\/978-0-387-98141-3"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-1-4939-3578-9_16","article-title":"Visualizing genomic data using Gviz and Bioconductor","volume":"1418","author":"Hahne","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Langfelder, P., and Horvath, S. (2008). WGCNA: An R package for weighted correlation network analysis. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-559"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/0042-6822(91)90437-G","article-title":"Genomic and subgenomic RNAs of rabbit hemorrhagic disease virus are both protein-linked and packaged into particles","volume":"184","author":"Meyers","year":"1991","journal-title":"Virology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e28318","DOI":"10.4161\/sgtp.28318","article-title":"Rho\u2019ing in and out of cells: Viral interactions with Rho GTPase signaling","volume":"5","author":"Jacob","year":"2014","journal-title":"Small GTPases"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"18360","DOI":"10.1073\/pnas.1110584108","article-title":"Natural killer (NK)\u2013dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4(+) T cells","volume":"108","author":"Nakayama","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nri3818","article-title":"The ins and outs of MHC class II-mediated antigen processing and presentation","volume":"15","author":"Roche","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"G1077","DOI":"10.1152\/ajpgi.00227.2012","article-title":"Advances in cholangiocyte immunobiology","volume":"303","author":"Syal","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.humpath.2012.07.018","article-title":"Expression of hepatocyte epidermal growth factor receptor, FAS and glypican 3 in EpCAM-positive regenerative clusters of hepatocytes, cholangiocytes, and progenitor cells in human liver failure","volume":"44","author":"Hattoum","year":"2013","journal-title":"Hum. Pathol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nri3084","article-title":"Towards a systems understanding of MHC class I and MHC class II antigen presentation","volume":"11","author":"Neefjes","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/S0168-8278(98)80149-9","article-title":"Expression and cytokine regulation of immune recognition elements by normal human biliary epithelial and established liver cell lines in vitro","volume":"29","author":"Cruickshank","year":"1998","journal-title":"J. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1056\/NEJM198906293202605","article-title":"Severe herpesvirus infections in an adolescent without natural killer cells","volume":"320","author":"Biron","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4009","DOI":"10.1182\/blood-2011-10-385377","article-title":"Bilateral adrenal EBV-associated smooth muscle tumors in a child with a natural killer cell deficiency","volume":"119","author":"Shaw","year":"2012","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fimmu.2015.00031","article-title":"NKp44 and natural cytotoxicity receptors as damage-associated molecular pattern recognition receptors","volume":"6","author":"Horton","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1016\/j.febslet.2011.04.032","article-title":"Why is PTPN22 a good candidate susceptibility gene for autoimmune disease?","volume":"585","author":"Burn","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1086\/422827","article-title":"A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis","volume":"75","author":"Begovich","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4049\/jimmunol.169.1.68","article-title":"Src-dependent Syk activation controls CD69-mediated signaling and function on human NK cells","volume":"169","author":"Pisegna","year":"2002","journal-title":"J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.4049\/jimmunol.171.8.4195","article-title":"The Rac-activating toxin cytotoxic necrotizing factor 1 oversees NK cell-mediated activity by regulating the actin\/microtubule interplay","volume":"171","author":"Malorni","year":"2003","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/ni.2467","article-title":"Re(de)fining the dendritic cell lineage","volume":"13","author":"Satpathy","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1182\/blood.V81.6.1607.1607","article-title":"Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins","volume":"81","author":"Holness","year":"1993","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1084\/jem.20120030","article-title":"Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages","volume":"209","author":"Satpathy","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"320","DOI":"10.4161\/cbt.2.4.451","article-title":"EpCAM: A new therapeutic target for an old cancer antigen","volume":"2","author":"Armstrong","year":"2003","journal-title":"Cancer Biol. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1034\/j.1600-0854.2002.31003.x","article-title":"Interferon-induced Mx proteins: Dynamin-like GTPases with antiviral activity","volume":"3","author":"Haller","year":"2002","journal-title":"Traffic"},{"key":"ref_89","first-page":"423","article-title":"Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: Correlation with monocyte infiltration","volume":"152","author":"Marra","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"967","DOI":"10.2353\/ajpath.2007.060441","article-title":"Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis","volume":"170","author":"Otogawa","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"481","DOI":"10.20506\/rst.10.2.553","article-title":"Vaccination against and immune response to viral haemorrhagic disease of rabbits: A review of research in the People\u2019s Republic of China","volume":"10","author":"Huang","year":"1991","journal-title":"Rev. Sci. Tech."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"13124","DOI":"10.1128\/JVI.05725-11","article-title":"Cardiotrophin-1 promotes a high survival rate in rabbits with lethal fulminant hepatitis of viral origin","volume":"85","author":"Tunon","year":"2011","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.vetmic.2013.12.015","article-title":"Spread of new variant RHDV in domestic rabbits on the Iberian Peninsula","volume":"169","author":"Dalton","year":"2014","journal-title":"Vet. Microbiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0167-5699(00)01699-6","article-title":"Viral mechanisms of immune evasion","volume":"21","author":"Alcami","year":"2000","journal-title":"Immunol. Today"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/319675a0","article-title":"Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy","volume":"319","author":"Karre","year":"1986","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Compans, R.W., Cooper, M.D., Honjo, T., Koprowski, H., Melchers, F., Oldstone, M.B.A., Olsnes, S., Potter, M., Vogt, P.K., and Wagner, H. (2006). NK Cell receptors involved in the response to human cytomegalovirus infection. Immunobiology of Natural Killer Cell Receptors, Springer.","DOI":"10.1007\/3-540-27743-9"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"McFadden, N., Bailey, D., Carrara, G., Benson, A., Chaudhry, Y., Shortland, A., Heeney, J., Yarovinsky, F., Simmonds, P., and Macdonald, A. (2011). Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002413"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.virol.2015.05.004","article-title":"Expression and partial characterisation of rabbit haemorrhagic disease virus non-structural proteins","volume":"484","author":"Urakova","year":"2015","journal-title":"Virology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1007\/s10530-016-1329-5","article-title":"High adaptive variability and virus-driven selection on major histocompatibility complex (MHC) genes in invasive wild rabbits in Australia","volume":"19","author":"Schwensow","year":"2017","journal-title":"Biol. Invasions"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/9\/512\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:21:27Z","timestamp":1760196087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/10\/9\/512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,19]]},"references-count":99,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["v10090512"],"URL":"https:\/\/doi.org\/10.3390\/v10090512","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,19]]}}}