Fiber2 and hexon genes are closely associated with the virulence of the emerging and highly pathogenic fowl adenovirus 4
| Autor: | Yuhan Zhang, Xia Yang, Hailong Wang, Youming Zhang, Kaiyue Tian, Jun Zhao, Zeng Wang, Gao Dongsheng, Ruxin Liu, Jun Fu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
China Genes Viral Genotype Virulence Factors Epidemiology Adenoviridae Infections Immunology Virulence Genome Viral Biology Microbiology Genome Article Recombineering Disease Outbreaks law.invention 03 medical and health sciences law Virology Drug Discovery Animals Vector (molecular biology) Gene Phylogeny Poultry Diseases Aviadenovirus Structural gene General Medicine 030104 developmental biology Infectious Diseases DNA Viral Recombinant DNA Capsid Proteins Parasitology Chickens |
| Zdroj: | Emerging Microbes & Infections |
| ISSN: | 2222-1751 |
| Popis: | Since May 2015, outbreaks of hydropericardium-hepatitis syndrome (HHS) caused by fowl adenovirus 4 (FAdV-4) with a novel genotype have been reported in China, causing significant economic losses to the poultry industry. A previous comparative analysis revealed that highly virulent FAdV-4 isolates contain various genomic deletions and multiple distinct mutations in the major structural genes fiber2 and hexon. To identify the genes responsible for the virulence of HHS-associated novel FAdV-4 isolates, FAdV-4 infectious clones were constructed by directly cloning the whole genome of a highly pathogenic FAdV-4 isolate (CH/HNJZ/2015) and that of a nonpathogenic strain (ON1) into a p15A-cm vector using the ExoCET method. Subsequently, the fiber2, hexon, and 1966-bp fragment-replaced mutant/recombinant viruses were constructed using Redαβ recombineering and ccdB counter-selection techniques. The pathogenicity of the rescued viruses was compared with that of the rescued parent viruses rHNJZ and rON1 in 3-week-old SPF chickens. Chickens infected with the rescued viruses carrying the fiber2 and/or hexon gene of the HNJZ strain developed similar clinical signs to the natural infection, with distinctive gross lesions and characteristic histological signs indicative of HHS observed in sick/dead chickens. Our results clearly demonstrated that the virulence of the novel highly pathogenic FAdV-4 strain was independent of the 1966-bp deletion and that the fiber2 and hexon genes have crucial roles in FAdV-4 pathogenicity. The data presented in this report will provide further insights into the crucial factors determining the pathogenicity of FAdV strains. Furthermore, the infectious clones generated based on the FAdV-4 genome can be used as a platform for studies of gene function and for the development of recombinant vaccines. |
| Databáze: | OpenAIRE |
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