{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T18:17:41Z","timestamp":1785608261257,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2017BC039"],"award-info":[{"award-number":["ZR2017BC039"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2015CM009"],"award-info":[{"award-number":["ZR2015CM009"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Construction of Subjects and Teams of Institue of Poultry Science","award":["CXGC2018E11"],"award-info":[{"award-number":["CXGC2018E11"]}]},{"name":"National Key Research and Development Plan","award":["2016YFD0501603-3"],"award-info":[{"award-number":["2016YFD0501603-3"]}]},{"DOI":"10.13039\/100014103","name":"Key Research and Development Plan of Shandong Province","doi-asserted-by":"publisher","award":["2018GSF121012"],"award-info":[{"award-number":["2018GSF121012"]}],"id":[{"id":"10.13039\/100014103","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agricultural Science and Technology Innovation Project of Shandong\u00a0Academy\u00a0of\u00a0Agricultural\u00a0Sciences","award":["CXGC2016A10"],"award-info":[{"award-number":["CXGC2016A10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Since mid-2015, numerous outbreaks of hydropericardium-hepatitis syndrome (HHS), which is caused by a novel fowl adenovirus serotype 4 (FAdV-4), have been reported in chickens in parts of China, thereby causing huge economic losses to the poultry industry. Thus, an effective vaccine to control the further spread of infections with this hyper-virulent FAdV-4 is imperative. In this study, we isolated a novel FAdV-4 strain SDJN0105 from a broiler farm with HHS disease in Shandong Province. Pathogenicity was evaluated by the observation of clinical symptoms, necropsy changes, and pathological tissue sections after oral and intramuscular (IM) infection of Specific pathogen free (SPF) chickens. The chickens infected by IM injection all died within three days, and chickens infected via the oculonasal route died within five days post-infection (dpi). Histopathological examination revealed that the pathology was confined to heart, liver, spleen, lung, kidney, and particularly the liver. Irrespective of the inoculation route, the highest viral DNA copy numbers were detected in the livers of infected chickens. The mRNA expression levels of IL-1\u03b2, IL-6, IL-8, IFNs, TNF-\u03b1, Mx, and OASL were significantly upregulated during the viral infection. In addition, an inactivated oil-emulsion FAdV-4 vaccine was developed. The vaccine could provide full protection for SPF chickens against a lethal dose of the FAdV-4 strain SDJN0105 and a high level of antibodies. These results improve our understanding of the innate immune responses in chickens infected with FAdV-4 and the pathogenesis of FAdV-4 caused by host factors, and the developed FAdV-4 vaccine is promising as a drug candidate for the prevention and reduction of the spread of HHS in poultry in China.<\/jats:p>","DOI":"10.3390\/v11070627","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T11:02:37Z","timestamp":1562583757000},"page":"627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Identification, Pathogenicity of Novel Fowl Adenovirus Serotype 4 SDJN0105 in Shandong, China and Immunoprotective Evaluation of the Newly Developed Inactivated Oil-emulsion FAdV-4 Vaccine"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2382-7161","authenticated-orcid":false,"given":"Kai","family":"Meng","sequence":"first","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Shandong Provincial Key Laboratory of Poultry Diseases Diagnosis and Immunology, Poultry Breeding Engineering Technology Center of Shandong Province, Jinan 250023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Shandong Provincial Key Laboratory of Poultry Diseases Diagnosis and Immunology, Poultry Breeding Engineering Technology Center of Shandong Province, Jinan 250023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Shandong Provincial Key Laboratory of Poultry Diseases Diagnosis and Immunology, Poultry Breeding Engineering Technology Center of Shandong Province, Jinan 250023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Ai","sequence":"additional","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Shandong Provincial Key Laboratory of Poultry Diseases Diagnosis and Immunology, Poultry Breeding Engineering Technology Center of Shandong Province, Jinan 250023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youling","family":"Wang","sequence":"additional","affiliation":[{"name":"Poultry Institute, Shandong Academy of Agricultural Sciences, Shandong Provincial Key Laboratory of Poultry Diseases Diagnosis and Immunology, Poultry Breeding Engineering Technology Center of Shandong Province, Jinan 250023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00140-16","DOI":"10.1128\/genomeA.00140-16","article-title":"Genome sequence of a fowl adenovirus serotype 4 strain lethal to chickens, isolated from china","volume":"4","author":"Li","year":"2016","journal-title":"Genome Announc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.micpath.2018.02.012","article-title":"Complete genome sequence and pathogenicity of fowl adenovirus serotype 4 involved in hydropericardium syndrome in southwest china","volume":"117","author":"Guan","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s13337-017-0372-x","article-title":"Cell-culture derived fowl adenovirus serotype 4 inactivated vaccine provides complete protection for virus infection on SPF chickens","volume":"28","author":"Du","year":"2017","journal-title":"Virusdisease"},{"key":"ref_4","first-page":"1","article-title":"A treatise on Angara disease (hydropericardium-pulmonary oedema-hepatonephritis syndrome)","volume":"34","author":"Jaffery","year":"1988","journal-title":"J. Pak. Vet. Med. Assoc."},{"key":"ref_5","first-page":"2","article-title":"Isolation of an adenovirus from hydropericardium syndrome in broiler chicks","volume":"1","author":"Khawaja","year":"1988","journal-title":"Pak. J. Vet. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1053\/rvsc.1999.0365","article-title":"Hydropericardium hepatitis syndrome of broiler poultry: Current status of research","volume":"68","author":"Ganesh","year":"2000","journal-title":"Res. Vet. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1099\/jgv.0.000567","article-title":"Hydropericardium syndrome outbreak caused by fowl adenovirus serotype 4 in China in 2015","volume":"97","author":"Niu","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.3382\/ps\/pex206","article-title":"Pathogenicity and immunosuppressive potential of fowl adenovirus in specific pathogen free chickens","volume":"96","author":"Niu","year":"2017","journal-title":"Poult. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1080\/03079459808419335","article-title":"Some strains of serotype 4 fowl adenoviruses cause inclusion body hepatitis and hydropericardium syndrome in chickens","volume":"27","author":"Mazaheri","year":"1998","journal-title":"Avian Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12985-016-0644-x","article-title":"Molecular epidemiology of hydropericardium syndrome outbreak-associated serotype 4 fowl adenovirus isolates in central China","volume":"13","author":"Zhang","year":"2016","journal-title":"Virol. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.vetmic.2016.11.005","article-title":"Characterization of fowl adenoviruses isolated between 2007 and 2014 in China","volume":"197","author":"Li","year":"2016","journal-title":"Vet. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tidona, C., and Darai, G. (2011). The Springer Index of Viruses, Springer Science & Business Media.","DOI":"10.1007\/978-0-387-95919-1"},{"key":"ref_13","first-page":"252","article-title":"Group I adenovirus infections","volume":"12","author":"Adair","year":"2008","journal-title":"Dis. Poult."},{"key":"ref_14","unstructured":"Benk\u00f6, M., Harrach, B., Both, G.W., Russell, W.C., Adair, B.M., Ad\u00e1m, E., de Jong, J.C., Hess, M., Johnson, M., and Kajon, A. (2005). Family Adenoviridae. Virus Taxonomy: Classification and Nomenclature of Viruses, Elsevier Academic Press."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1128\/CMR.00052-07","article-title":"Adenoviruses in immunocompromised hosts","volume":"21","author":"Echavarria","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6009","DOI":"10.3390\/v7112923","article-title":"Oncolytic adenovirus: Strategies and insights for vector design and immuno-oncolytic applications","volume":"7","author":"Uusikerttula","year":"2015","journal-title":"Viruses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1128\/JCM.01567-08","article-title":"Classifcation of fowl adenovirus serotypes by use of high-resolution melting-curve analysis of the hexon gene region","volume":"47","author":"Steer","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"803","DOI":"10.3382\/ps\/pex338","article-title":"Molecular epidemiology and phylogenetic analysis of fowl adenoviruses caused hydropericardium outbreak in China during 2015","volume":"97","author":"Niu","year":"2018","journal-title":"Poult. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1042\/BST0351437","article-title":"Building an immune system from nine domains","volume":"35","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nri2690","article-title":"Intracellular DNA recognition","volume":"10","author":"Hornung","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.3389\/fmicb.2017.01005","article-title":"Different dynamic distribution in chickens and ducks of the hypervirulent, novel genotype fowl adenovirus serotype 4 recently emerged in China","volume":"8","author":"Pan","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1038\/emi.2016.50","article-title":"Outbreaks of serotype 4 fowl adenovirus with novel genotype, China","volume":"5","author":"Ye","year":"2016","journal-title":"Emerg. Microbes Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1637\/11671-050817-RegR","article-title":"Phylogenetic analyses of Fowl Adenoviruses (FAdV) isolated in China and pathogenicity of a FAdV-8 isolate","volume":"61","author":"Ruan","year":"2017","journal-title":"Avian Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1637\/11758-100917-Reg.1","article-title":"Recombinant Fiber-2 protein-based indirect ELISA for antibody detection of fowl adenovirus serotype 4","volume":"62","author":"He","year":"2018","journal-title":"Avian Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fimmu.2018.00049","article-title":"Fowl adenovirus serotype 4 SD0828 infections causes high mortality rate and cytokine levels in specific pathogen-free chickens compared to ducks","volume":"9","author":"Li","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/03079450050045440","article-title":"Detection and differentiation of avian adenoviruses: A review","volume":"29","author":"Hess","year":"2000","journal-title":"Avian Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1080\/03079450310001652086","article-title":"Phylogenetic analysis of fowl adenoviruses","volume":"33","author":"Meulemans","year":"2004","journal-title":"Avian Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1016\/j.vaccine.2014.03.015","article-title":"An inactivated oil-emulsion fowl adenovirus serotype 4 vaccine provides broad cross-protection against various serotypes of fowl adenovirus","volume":"32","author":"Kim","year":"2014","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s11259-007-9034-6","article-title":"The role of chicken IL-1\u03b2, IL-6 and TNF-\u03b1 in the occurrence of amyloid arthropathy","volume":"32","author":"Sevimli","year":"2008","journal-title":"Vet. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3382\/ps\/pew229","article-title":"ALV-J strain SCAU-HN06 induces innate immune responses in chicken primary monocyte-derived macrophages","volume":"96","author":"Feng","year":"2017","journal-title":"Poult. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.dci.2004.08.002","article-title":"Recombinant chicken IL-6 does not activate heterophils isolated from day-old chickens in vitro","volume":"29","author":"Ferro","year":"2005","journal-title":"Dev. Comp. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"83938","DOI":"10.18632\/oncotarget.13728","article-title":"Interleukin-8 holds promise to serve as a molecular adjuvant in DNA vaccination model against Streptococcus iniae infection in fish","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2008.03.036","article-title":"TNF-\u03b1 induces two distinct caspase-8 activation pathways","volume":"133","author":"Wang","year":"2008","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.celrep.2016.11.083","article-title":"Opposing functions of microglial and macrophagic TNFR2 in the pathogenesis of experimental autoimmune Encephalomyelitis","volume":"18","author":"Gao","year":"2017","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bhargava, R., Janssen, W., Altmann, C., Andr\u00e9s-Hernando, A., Okamura, K., Vandivier, R.W., Ahuja, N., and Faubel, S. (2013). Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061405"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pan, Q., Yang, Y., Gao, Y., Qi, X., Liu, C., Zhang, Y., Cui, H., and Wang, X. (2017). An inactivated novel genotype fowl adenovirus 4 protects chickens against the hydropericardium syndrome that recently emerged in China. Viruses, 9.","DOI":"10.3390\/v9080216"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/7\/627\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:03:36Z","timestamp":1760187816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/7\/627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,8]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["v11070627"],"URL":"https:\/\/doi.org\/10.3390\/v11070627","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,8]]}}}