Abstract

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-1β, IL-6, IL-8, IFNs, TNF-α, 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.

Highlights

  • Fowl adenovirus serotype 4 (FAdV-4), which is a non-enveloped, double-stranded linear DNA virus, plays an important role in the etiology of the disease in chickens called hydropericardium-hepatitis syndrome (HHS) [1,2,3]

  • The vaccine could provide full protection for Specific pathogen free (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

  • We investigated the pathogenicity of FAdV-4 in SPF chickens

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Summary

Introduction

Fowl adenovirus serotype 4 (FAdV-4), which is a non-enveloped, double-stranded linear DNA virus, plays an important role in the etiology of the disease in chickens called hydropericardium-hepatitis syndrome (HHS) [1,2,3]. HHS is a severe disease that can cause 30–80% mortality in chickens aged 3–6 weeks [6]. The main feature in HHS-affected chickens was the accumulation of transparent or straw-colored liquid in the pericardial sac and damage to the heart. Viruses 2019, 11, 627 been observed in the lungs, livers, and kidneys. Histological studies have revealed that multifocal lesions necrosis and mononuclear cell infiltration often occur in the liver of the infected chickens [7,8,9]

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