Duck hepatitis A virus (DHAV) is one of the pathogens that cause fatal duck viral hepatitis (DVH) in ducklings, which is an acute and contagious disease with a high mortality rate. Despite a continuing official duck vaccination program, DHAV infection remains a major threat to the duck industry. Considerable changes were observed in the epidemiology of DHAV-1/-3 in China over time. Therefore, comparing the pathogenicity of different DHAV serotypes can provide a theoretical basis for the diagnosis and prevention of DVH. In this study, we systematically investigated the effects of infection with DHAV-1/-3 field strains on clinical signs, gross lesions, histopathological changes, viral RNA detection, enzymatic systems, and metabolite concentrations. The results demonstrated that the major macroscopic and microscopic lesions in ducks infected with DHAV-1/-3 in the liver, brain, spleen, pancreas, and kidneys exhibited no significant differences. After 24 h of infection, DHAV quickly appeared in blood and major organs. Significant changes in clinical chemical markers together with histopathological lesions and viral RNA detection indicated that the liver is the major target organ for both viruses, resulting in impaired of liver integrity and function. In addition, we found that both viruses were able to invade both central and peripheral immune organs. Also lipase plasma activity was substantially affected by DHAV-1/-3, indicating that the integrity and function of the pancreas was compromised. However, there was no significant difference in pathogenicity between DHAV-1 and -3. The results of this study provide new insights into the pathogenesis of DHAV-1/3, two viruses that cause serious depression, metabolic disorders, and immunosuppression.

Fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium syndrome. To clarify the effects of FAdV-4 on immune organs in birds, we conducted a detailed examination of dynamic morphology and damage mechanisms in chickens randomly divided into 4 groups (FAdV-4, vaccination, FAdV-4 plus vaccination, and control). FAdV-4 caused the depletion of lymphocytes and subsequent growth impairment in the thymus and bursa. Chickens infected with FAdV-4 and subjected to vaccination experienced greater inhibition of antibody responses to inactivated vaccines against Newcastle disease and avian influenza virus subtype H9 than uninfected and vaccinated chickens. The mechanisms underlying adenovirus-mediated lymphoid organ damage were further investigated via transferase-mediated dUTP nick-end labeling and apoptotic genes transcription analyses. Notably, lymphocytes apoptosis in lymphoid organs and expression of specific gene transcripts was significantly upregulated after infection (P < 0.05). Furthermore, increased expression of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α mRNA was observed (P < 0.05), compared to the control group. Our collective findings suggested that FAdV-4 caused structural and functional damage of immune organs via apoptosis along with induction of a severe inflammatory response.

Serotype 4 fowl adenovirus (FAdV-4) is the main pathogen for hydropericardium syndrome (HPS) in chickens. It has caused major economic losses in the global poultry industry. Currently, FAdV-4′s transmission routes in chickens remain unclear. Here we investigate the airborne transmission routes of FAdV-4 in chickens. A total of 45 ten-day-old chickens were equally divided into three groups (infected group/isolator A, airborne group/isolator B, and control group/isolator C). Of note, isolators A and B were connected by a leak-free pipe. The results showed that the virus could form a viral aerosol, detected in isolators two days post infection (dpi). The viral aerosol reached a peak at 4 dpi in the infected group. Healthy chickens in the airborne group were infected by the virus at 8 dpi. The chickens of the airborne group demonstrated subclinical symptoms capable of shedding the virus for some time. This finding suggests that FAdV-4 can be efficiently transmitted among chickens by aerosol transmission. These findings have significant implications for developing strategies to control this infectious disease epidemic.

Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly right ventricular involvement. ACM is one of the major conditions associated with an increased risk of sudden cardiac death, most notably in young individuals and athletes. ACM has strong genetic determinants, and genetic variants in more than 25 genes have been identified to be associated with ACM, accounting for approximately 60% of ACM cases. Genetic studies of ACM in vertebrate animal models such as zebrafish (Danio rerio), which are highly amenable to large-scale genetic and drug screenings, offer unique opportunities to identify and functionally assess new genetic variants associated with ACM and to dissect the underlying molecular and cellular mechanisms at the whole-organism level. Here, we summarize key genes implicated in ACM. We discuss the use of zebrafish models, categorized according to gene manipulation approaches, such as gene knockdown, gene knock-out, transgenic overexpression, and CRISPR/Cas9-mediated knock-in, to study the genetic underpinning and mechanism of ACM. Information gained from genetic and pharmacogenomic studies in such animal models can not only increase our understanding of the pathophysiology of disease progression, but also guide disease diagnosis, prognosis, and the development of innovative therapeutic strategies.