Abstract
Hydropericardium-Hepatitis Syndrome (HHS) caused by Fowl Adenovirus Serotype 4 (FAdV4) infection is a severe threat to the poultry industry worldwide, especially in China since 2015. Recent studies show that FAdV4 induces liver injury through apoptosis. However, the underlying molecular mechanism is still unclear. We report here that FAdV4 infection caused apoptosis in Leghorn male hepatocellular (LMH) cells and that PX, a structural protein of FAdV4, acted as a major viral factor inducing apoptosis. Furthermore, the nuclear localization of PX is determined by the R/K regions of PX and required for PX-induced apoptosis. Moreover, alanines 11 and 129 of PX are crucial to PX-induced apoptosis. Inhibition of FAdV4-induced apoptosis by caspase inhibitors retarded viral replication, suggesting that PX serves as a virulence factor for FAdV4 infection, which may further our understandings of the pathogenesis of FAdV4 infection.
Highlights
Adenoviruses are widely-distributed microbes across the globe, and can infect varied species of vertebrates, including birds, animals and humans
To further analyze the cell biological features associated with Fowl Adenovirus serotype 4 (FAdV4)-induced cytopathic effect (CPE) in Leghorn Male Hepatocellular (LMH) cells, samples stained for Annexin V-PE and 7-AAD were analyzed by flow cytometry
The number of Annexin V-positive cells could be markedly reduced by caspase inhibitors (z-VAD-fmk, pan-caspase inhibitor; z-DEVD-fmk, caspase-3 inhibitor and z-IETD-fmk, caspase-8 inhibitor) except z-LEHD-fmk, the caspase-9 inhibitor (Figure 1e,f). These results demonstrate that infection of LMH cells with FAdV4 induced apoptosis in host cells
Summary
Adenoviruses are widely-distributed microbes across the globe, and can infect varied species of vertebrates, including birds, animals and humans. Fowl adenoviruses, belonging to the Aviadenovirus genus in the Adenoviridae family, can be divided into 12 serotypes, including FAdV1-7, FAdV8a/b, and FAdV9-12. Fowl Adenovirus serotype 4 (FAdV4), mainly infects 3- to 6-week old broilers [1]. Hepatitis-hydropericardium syndrome (HHS) was observed in the diseased chickens with FAdV4 infection clinically characterized by swollen livers with focal necroses and petechial hemorrhages, as well as enlarged pericardial sacs containing clear and yellowish fluids. FAdV4 has caused numerous outbreaks of HHS in chickens in China, leading to severe economic losses to the stakeholders. FAdV4 is a double-stranded DNA (dsDNA) virus, and its genome, 43.7 kb, encodes approximately
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