Since May 2015, severe outbreaks of hepatitis-hydropericardium syndrome (HHS) associated with infections of fowl aviadenovirus (FAdV) have emerged in broiler chickens in several Chinese provinces. ...

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.

Since 2015, severe outbreaks of hepatitis-hydropericardium syndrome (HHS), caused by hypervirulent fowl adenovirus serotype 4 (FAdV-4), have emerged in several provinces in China, posing a great threat to poultry industry. So far, factors contributing to the pathogenesis of hypervirulent FAdV-4 have not been fully uncovered. Elucidation of the pathogenesis of FAdV-4 will facilitate the development of effective FAdV-4 vaccine candidates for the control of HHS and vaccine vector. The interaction between pathogen and host defense system determines the pathogenicity of the pathogen. Therefore, the present review highlights the knowledge of both viral and host factors contributing to the pathogenesis of hypervirulent FAdV-4 strains to facilitate the related further studies.