Fiber2 and hexon genes are closely associated with the virulence of the emerging and highly pathogenic fowl adenovirus 4

毒力 生物 病毒学 基因 基因组 遗传学 微生物学
作者
Yuhan Zhang,Ruxin Liu,Kaiyue Tian,Zeng Wang,Xia Yang,Dongsheng Gao,Youming Zhang,Jun Fu,Hailong Wang,Jun Zhao
出处
期刊:Emerging microbes & infections [Taylor & Francis]
卷期号:7 (1): 1-10 被引量:68
标识
DOI:10.1038/s41426-018-0203-1
摘要

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.
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