{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:22:48Z","timestamp":1780420968857,"version":"3.54.1"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture, Agricultural Research Service, National Program 103 Animal Health","doi-asserted-by":"publisher","award":["3020-32000-020-00D"],"award-info":[{"award-number":["3020-32000-020-00D"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture, Agricultural Research Service, National Program 103 Animal Health","doi-asserted-by":"publisher","award":["58-3020-7-024"],"award-info":[{"award-number":["58-3020-7-024"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Colorado State University","award":["3020-32000-020-00D"],"award-info":[{"award-number":["3020-32000-020-00D"]}]},{"name":"Colorado State University","award":["58-3020-7-024"],"award-info":[{"award-number":["58-3020-7-024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Bluetongue (BT) is a Culicoides midge-borne hemorrhagic disease affecting cervids and ruminant livestock species, resulting in significant economic losses from animal production and trade restrictions. Experimental animal infections using the \u03b1\/\u03b2 interferon receptor knockout IFNAR mouse model and susceptible target species are critical for understanding viral pathogenesis, virulence, and evaluating vaccines. However, conducting experimental vector-borne transmission studies with the vector itself are logistically difficult and experimentally problematic. Therefore, experimental infections are induced by hypodermic injection with virus typically derived from baby hamster kidney (BHK) cells. Unfortunately, for many U.S. BTV serotypes, it is difficult to replicate the severity of the disease seen in natural, midge-transmitted infections by injecting BHK-derived virus into target host animals. Using the IFNAR BTV murine model, we compared the virulence of traditional BHK cell-derived BTV-17 with C.\u00a0sonorensis midge (W8) cell-derived BTV-17 to determine whether using cells of the transmission vector would provide an in vitro virulence aspect of vector-transmitted virus. At both low and high doses, mice inoculated with W8-BTV-17 had an earlier onset of viremia, earlier onset and peak of clinical signs, and significantly higher mortality compared to mice inoculated with BHK-BTV-17. Our results suggest using a Culicoides W8 cell-derived inoculum may provide an in vitro vector-enhanced infection to more closely represent disease levels seen in natural midge-transmitted infections while avoiding the logistical and experimental complexity of working with live midges.<\/jats:p>","DOI":"10.3390\/v16091474","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:51:43Z","timestamp":1726620703000},"page":"1474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Increased Virulence of Culicoides Midge Cell-Derived Bluetongue Virus in IFNAR Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7414-4512","authenticated-orcid":false,"given":"Barbara S.","family":"Drolet","sequence":"first","affiliation":[{"name":"Arthropod-Borne Animal Diseases Research Unit, Agricultural Research Service, United States Department of Agriculture, Manhattan, KS 66502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-3898","authenticated-orcid":false,"given":"Lindsey","family":"Reister-Hendricks","sequence":"additional","affiliation":[{"name":"Arthropod-Borne Animal Diseases Research Unit, Agricultural Research Service, United States Department of Agriculture, Manhattan, KS 66502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie","family":"Mayo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Pathology, Colorado State University, 1601 Campus Delivery, Fort Collins, CO 80526, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Case","family":"Rodgers","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Pathology, Colorado State University, 1601 Campus Delivery, Fort Collins, CO 80526, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Molik","sequence":"additional","affiliation":[{"name":"Arthropod-Borne Animal Diseases Research Unit, Agricultural Research Service, United States Department of Agriculture, Manhattan, KS 66502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8321-3287","authenticated-orcid":false,"given":"David Scott","family":"McVey","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, P.O. Box 830905, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/bs.aivir.2017.08.003","article-title":"Bluetongue Virus: From BTV-1 to BTV-27","volume":"99","author":"Belbis","year":"2017","journal-title":"Adv. Virus Res."},{"key":"ref_2","unstructured":"USDA-APHIS (2022, December 15). Bluetongue, Available online: https:\/\/www.aphis.usda.gov\/livestock-poultry-disease\/cattle\/bluetongue."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.2460\/javma.1995.206.09.1322","article-title":"Pathogenesis of bluetongue virus infection of cattle","volume":"206","author":"MacLachlan","year":"1995","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1051\/vetres:2008023","article-title":"Bluetongue virus: Virology, pathogenesis and immunity","volume":"39","author":"Mertens","year":"2008","journal-title":"Vet. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Calvo-Pinilla, E., Rodriguez-Calvo, T., Anguita, J., Sevilla, N., and Ortego, J. (2009). Establishment of a bluetongue virus infection model in mice that are deficient in the alpha\/beta interferon receptor. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005171"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1099\/vir.0.024117-0","article-title":"Experimental oral infection of bluetongue virus serotype 8 in type I interferon receptor-deficient mice","volume":"91","author":"Nieto","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.virusres.2013.09.038","article-title":"Interferon alpha\/beta receptor knockout mice as a model to study bluetongue virus infection","volume":"182","author":"Ortego","year":"2014","journal-title":"Virus Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11479","DOI":"10.1128\/JVI.05226-11","article-title":"Determinants of Bluetongue Virus Virulence in Murine Models of Disease","volume":"85","author":"Caporale","year":"2011","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.virusres.2013.12.044","article-title":"A review of experimental infections with bluetongue virus in the mammalian host","volume":"182","author":"Coetzee","year":"2014","journal-title":"Virus Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1136\/vr.161.8.253","article-title":"Clinical signs and pathology shown by British sheep and cattle infected with bluetongue virus serotype 8 derived from the 2006 outbreak in northern Europe","volume":"161","author":"Darpel","year":"2007","journal-title":"Vet. Rec."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1024\/0036-7281.150.10.491","article-title":"Bluetongue disease in Swiss sheep breeds: Clinical signs after experimental infection with bluetongue virus serotype 8","volume":"150","author":"Worwa","year":"2008","journal-title":"Schweiz. Arch. Tierheilkd."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.vetmic.2008.11.012","article-title":"Experimental reproduction of bluetongue virus serotype 8 clinical disease in calves","volume":"136","author":"Guyot","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.vetmic.2010.05.004","article-title":"Infectious blood or culture-grown virus: A comparison of bluetongue virus challenge models","volume":"146","author":"Eschbaumer","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.vetmic.2010.01.011","article-title":"Virological and pathological findings in Bluetongue virus serotype 8 infected sheep","volume":"144","author":"Worwa","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1089\/vbz.2015.1924","article-title":"European bluetongue serotype 8: Disease threat assessment for U.S. sheep","volume":"16","author":"Drolet","year":"2016","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1365-2915.2008.00732.x","article-title":"Rates of bluetongue virus transmission between Culicoides sonorensis and sheep","volume":"22","author":"Baylis","year":"2008","journal-title":"Med. Vet. Entomol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1354\/vp.45-3-310","article-title":"Experimental reproduction of severe bluetongue in sheep","volume":"45","author":"MacLachlan","year":"2008","journal-title":"Vet. Pathol."},{"key":"ref_18","first-page":"379","article-title":"Effect of Culicoides sonorensis salivary proteins on clinical disease outcome in experimental bluetongue virus serotype 8 infection of Dorset sheep","volume":"51","author":"Drolet","year":"2015","journal-title":"Vet. Ital."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.vetmic.2013.05.027","article-title":"Experimental infection of white-tailed deer (Odocoileus virginianus) with Northern European bluetongue virus serotype 8","volume":"166","author":"Drolet","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13567-016-0357-6","article-title":"Experimental bluetongue virus superinfection in calves previously immunized with bluetongue virus serotype 8","volume":"47","author":"Martinelle","year":"2016","journal-title":"Vet. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e251","DOI":"10.1111\/tbed.12780","article-title":"Bluetongue virus serotype 27: Experimental infection of goats, sheep and cattle with three BTV-27 variants reveal atypical characteristics and likely direct contact transmission BTV-27 between goats","volume":"65","author":"Breard","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13567-018-0556-4","article-title":"Assessment of cross-protection induced by a bluetongue virus (BTV) serotype 8 vaccine towards other BTV serotypes in experimental conditions","volume":"49","author":"Martinelle","year":"2018","journal-title":"Vet. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e243","DOI":"10.1111\/tbed.12746","article-title":"Experimental infection of sheep, goats and cattle with a bluetongue virus serotype 4 field strain from Bulgaria, 2014","volume":"65","author":"Schulz","year":"2018","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.14202\/vetworld.2019.41-47","article-title":"Infection kinetics and antibody responses in Deccani sheep during experimental infection and superinfection with bluetongue virus serotypes 4 and 16","volume":"12","author":"Putty","year":"2019","journal-title":"Vet. World"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"199246","DOI":"10.1016\/j.virusres.2023.199246","article-title":"Monitoring longitudinal immunological responses to bluetongue virus 17 in experimentally infected sheep","volume":"338","author":"Westrich","year":"2023","journal-title":"Virus Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.vetimm.2011.03.005","article-title":"A comparison of intradermal and intravenous inoculation of bluetongue virus serotype 23 in sheep for clinico-pathology, and viral and immune responses","volume":"141","author":"Umeshappa","year":"2011","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1111\/tbed.13131","article-title":"Evidence of reduced viremia, pathogenicity and vector competence in a re-emerging European strain of bluetongue virus serotype 8 in sheep","volume":"66","author":"Flannery","year":"2019","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.vaccine.2014.11.053","article-title":"Evaluation of adaptive immune responses and heterologous protection induced by inactivated bluetongue virus vaccines","volume":"33","author":"Breard","year":"2015","journal-title":"Vaccine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.vetmic.2009.04.003","article-title":"Transplacental and oral transmission of wild-type bluetongue virus serotype 8 in cattle after experimental infection","volume":"138","author":"Backx","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.vetmic.2010.03.012","article-title":"Experimental infection of European red deer (Cervus elaphus) with bluetongue virus serotypes 1 and 8","volume":"145","author":"Falconi","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Darpel, K.E., Barber, J., Hope, A., Wilson, A.J., Gubbins, S., Henstock, M., Frost, L., Batten, C., Veronesi, E., and Moffat, K. (2016). Using shared needles for subcutaneous inoculation can transmit bluetongue virus mechanically between ruminant hosts. Sci. Rep., 6.","DOI":"10.1038\/srep20627"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.vetmic.2016.07.013","article-title":"Experimental infection of small ruminants with bluetongue virus expressing Toggenburg Orbivirus proteins","volume":"192","year":"2016","journal-title":"Vet. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e426","DOI":"10.7717\/peerj.426","article-title":"The salivary secretome of the biting midge, Culicoides sonorensis","volume":"2","author":"Lehiy","year":"2014","journal-title":"PeerJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1186\/s13071-018-2935-0","article-title":"Physiological and immunological responses to Culicoides sonorensis blood-feeding: A murine model","volume":"11","author":"Lehiy","year":"2018","journal-title":"Parasit. Vectors"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"955","DOI":"10.2460\/javma.237.8.955","article-title":"Investigation of a bluetongue disease epizootic caused by bluetongue virus serotype 17 in sheep in Wyoming","volume":"237","author":"Miller","year":"2010","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1603\/0022-2585-40.3.348","article-title":"Characterization of cell lines developed from field populations of Culicoides sonorensis (Diptera: Ceratopogonidae)","volume":"40","author":"McHolland","year":"2003","journal-title":"J. Med. Entomol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1093\/bja\/71.6.885","article-title":"Anaesthesia of animals for biomedical research","volume":"71","author":"Flecknell","year":"1993","journal-title":"Br. J. Anaesth."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1177\/104063870701900103","article-title":"Performance of a foot-and-mouth disease virus reverse transcription-polymerase chain reaction with amplification controls between three real-time instruments","volume":"19","author":"Moniwa","year":"2007","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1177\/104063879200400405","article-title":"Detection of bluetongue virus serogroup by polymerase chain reaction","volume":"4","author":"Akita","year":"1992","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Carpenter, M., Kopanke, J., Lee, J., Rodgers, C., Reed, K., Sherman, T.J., Graham, B., Stenglein, M., and Mayo, C. (2024). Assessing Reassortment between Bluetongue Virus Serotypes 10 and 17 at Different Coinfection Ratios in Culicoides sonorensis. Viruses, 16.","DOI":"10.3390\/v16020240"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kopanke, J.H., Lee, J.S., Stenglein, M.D., and Mayo, C.E. (2020). The Genetic Diversification of a Single Bluetongue Virus Strain Using an In Vitro Model of Alternating-Host Transmission. Viruses, 12.","DOI":"10.3390\/v12091038"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1128\/jvi.10.4.783-794.1972","article-title":"Structure of the bluetongue virus capsid","volume":"10","author":"Verwoerd","year":"1972","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.fob.2015.02.001","article-title":"Structure-based identification of functional residues in the nucleoside-2\u2032-O-methylase domain of Bluetongue virus VP4 capping enzyme","volume":"5","author":"Stewart","year":"2015","journal-title":"FEBS Open Bio"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9832","DOI":"10.1128\/JVI.73.12.9832-9842.1999","article-title":"Expression and functional characterization of bluetongue virus VP2 protein: Role in cell entry","volume":"73","author":"Hassan","year":"1999","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Kar, A.K., Bhattacharya, B., and Roy, P. (2007). Bluetongue virus RNA binding protein NS2 is a modulator of viral replication and assembly. BMC Mol. Biol., 8.","DOI":"10.1186\/1471-2199-8-4"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1099\/vir.0.18705-0","article-title":"A possible overwintering mechanism for bluetongue virus in the absence of the insect vector","volume":"84","author":"Takamatsu","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcpa.2009.04.003","article-title":"The pathology and pathogenesis of bluetongue","volume":"141","author":"MacLachlan","year":"2009","journal-title":"J. Comp. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/BF01321058","article-title":"The pathogenesis of bluetongue virus infection of bovine blood cells in vitro: Ultrastructural characterization","volume":"136","author":"Brewer","year":"1994","journal-title":"Arch. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/0022-2011(89)90123-7","article-title":"Cell lines from Culicoides variipennis (Diptera: Ceratopogonidae) support replication of bluetongue virus","volume":"54","author":"Wechsler","year":"1989","journal-title":"J. Invertebr. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.7150\/ijbs.14967","article-title":"Pathological Characterization Of IFNAR(-\/-) Mice Infected With Bluetongue Virus Serotype 4","volume":"12","author":"Bermudez","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1126\/science.8009221","article-title":"Functional role of type I and type II interferons in antiviral defense","volume":"264","author":"Muller","year":"1994","journal-title":"Science"},{"key":"ref_52","first-page":"3","article-title":"Type I interferon receptor knockout mice as models for infection of highly pathogenic viruses with outbreak potential","volume":"39","author":"Wong","year":"2018","journal-title":"Zool. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Castillo-Olivares, J., Calvo-Pinilla, E., Casanova, I., Bachanek-Bankowska, K., Chiam, R., Maan, S., Nieto, J.M., Ortego, J., and Mertens, P.P. (2011). A modified vaccinia Ankara virus (MVA) vaccine expressing African horse sickness virus (AHSV) VP2 protects against AHSV challenge in an IFNAR -\/- mouse model. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016503"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.7150\/ijbs.95275","article-title":"IFNAR(-\/-) Mice Constitute a Suitable Animal Model for Epizootic Hemorrhagic Disease Virus Study and Vaccine Evaluation","volume":"20","author":"Anguita","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8356","DOI":"10.1128\/JVI.75.18.8356-8367.2001","article-title":"Expression and functional characterization of bluetongue virus VP5 protein: Role in cellular permeabilization","volume":"75","author":"Hassan","year":"2001","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0042-6822(83)90000-4","article-title":"Glycosylation of the major outer capsid protein of bluetongue viruses","volume":"194","author":"Yang","year":"1993","journal-title":"Virology"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lago, B.V., Portilho, M.M., Mello, V.M., De Sousa, P.S.F., Angelice, G.P., Marques, B.C.L., da Silva Andrade, L.T., Marques, V.A., Lewis-Ximenez, L.L., and Mello, F. (2024). Genetic variability of hepatitis B virus in acute and in different phases of chronic infection in Brazil. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-60900-2"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Nam, B., Mekuria, Z., Carossino, M., Li, G., Zheng, Y., Zhang, J., Cook, R.F., Shuck, K.M., Campos, J.R., and Squires, E.L. (2019). Intrahost Selection Pressure Drives Equine Arteritis Virus Evolution during Persistent Infection in the Stallion Reproductive Tract. J. Virol., 93.","DOI":"10.1128\/JVI.00045-19"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1099\/vir.0.000149","article-title":"Intensive temporal mapping of hepatitis C hypervariable region 1 quasispecies provides novel insights into hepatitis C virus evolution in chronic infection","volume":"96","author":"Crosbie","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Caporale, M., Di Gialleonorado, L., Janowicz, A., Wilkie, G., Shaw, A., Savini, G., Van Rijn, P.A., Mertens, P., Di Ventura, M., and Palmarini, M. (2014). Virus and Host Factors Affecting the Clinical Outcome of Bluetongue Virus Infection. J. Virol.","DOI":"10.1128\/JVI.01641-14"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetmic.2012.07.007","article-title":"Bluetongue virus genetic and phenotypic diversity: Towards identifying the molecular determinants that influence virulence and transmission potential","volume":"161","author":"Coetzee","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8298","DOI":"10.1128\/JVI.75.17.8298-8305.2001","article-title":"Occurrence of genetic drift and founder effect during quasispecies evolution of the VP2 and NS3\/NS3A genes of bluetongue virus upon passage between sheep, cattle, and Culicoides sonorensis","volume":"75","author":"Bonneau","year":"2001","journal-title":"J. Virol."},{"key":"ref_63","first-page":"441","article-title":"Delayed hypersensitivity in cattle after vaccination against foot- and mouth-disease: Isolation of a sensitizing lipoprotein from BHK 21 cells","volume":"141","author":"Kaaden","year":"1971","journal-title":"Z. Immunitatsforsch. Exp. Klin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1017\/S0022172400024232","article-title":"The evaluation of hypersensitivity tests in cattle after foot-and-mouth disease vaccination","volume":"74","author":"Black","year":"1975","journal-title":"J. Hyg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1136\/vr.100.10.195","article-title":"Allergy in cattle after foot-and-mouth disease vaccination","volume":"100","author":"Black","year":"1977","journal-title":"Vet. Rec."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Rodriguez-Martin, D., Louloudes-Lazaro, A., Avia, M., Martin, V., Rojas, J.M., and Sevilla, N. (2021). The Interplay between Bluetongue Virus Infections and Adaptive Immunity. Viruses, 13.","DOI":"10.3390\/v13081511"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Morales-Hojas, R., Hinsley, M., Armean, I.M., Silk, R., Harrup, L.E., Gonzalez-Uriarte, A., Veronesi, E., Campbell, L., Nayduch, D., and Saski, C. (2018). The genome of the biting midge Culicoides sonorensis and gene expression analyses of vector competence for bluetongue virus. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5014-1"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/9\/1474\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:57:43Z","timestamp":1760111863000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/9\/1474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,17]]},"references-count":67,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["v16091474"],"URL":"https:\/\/doi.org\/10.3390\/v16091474","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,17]]}}}