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Identification of chicken CAR homology as a cellular receptor for the emerging highly pathogenic fowl adenovirus 4 via unique binding mechanism.

ABSTRACT: Since 2015, the prevalence of severe hepatitis-hydropericardium syndrome, which is caused by the novel genotype fowl adenovirus serotype 4 (FAdV-4), has increased in China and led to considerable economic losses. The replication cycle of FAdV-4, especially the emerging highly pathogenic novel genotype FAdV-4, remains largely unknown. The adenovirus fibre interacts with the cellular receptor as the initial step in adenovirus (AdV) infection. In our previous studies, the complete genome sequence showed that the fibre patterns of FAdV-4 were distinct from all other AdVs. Here, protein-blockage and antibody-neutralization assays were performed to confirm that the novel FAdV-4 short fibre was critical for binding to susceptible leghorn male hepatocellular (LMH) cells. Subsequently, fibre 1 was used as bait to investigate the receptor on LMH cells via mass spectrometry. The chicken coxsackie and adenovirus receptor (CAR) protein was confirmed as the novel FAdV-4 receptor in competition assays. We further identified the D2 domain of CAR (D2-CAR) as the active domain responsible for binding to the short fibre of the novel FAdV-4. Taken together, these findings demonstrate for the first time that the chicken CAR homolog is a cellular receptor for the novel FAdV-4, which facilitates viral entry by interacting with the viral short fibre through the D2 domain. Collectively, these findings provide an in-depth understanding of the mechanisms of the emerging novel genotype FAdV-4 invasion and pathogenesis.

SUBMITTER: Pan Q

PROVIDER: S-EPMC7144210 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe livestock sector contributes 1.90% to the GDP in Bangladesh during 2021-22. Poultry is one of the important subsectors struggling with diseases. Fowl adenoviruses (FAdVs) cause numerous diseases resulting in economic losses to the poultry industry worldwide. Several FAdV serotypes cause inclusion body hepatitis in chicken. Although FAdV infection was suspected, there was no confirmatory report from Bangladesh. The study was conducted to investigate the FAdV infection and antibodies in chicken.MethodsA total of 50 samples, each composed of liver and spleen, were collected from different chickens of Gazipur, Dinajpur, and Panchagarh district. Each location belongs to A, B, and C poultry zones of Bangladesh, respectively. Viruses were detected by real-time PCR and conventional PCR. Blood samples (n = 303) were collected at the beginning and after the recovery from infection and tested by indirect ELISA. Sequencing of PCR products was done for serotyping and phylogenetic analysis.ResultsClinical signs were observed including anorexia, drowsiness, ruffled feathers, reduced body weight, lack of uniformity, and high mortality (15-25%). Enlarged friable liver with yellow to tan color mottled with the focal soft area, fluid in pericardial sac, swollen and hemorrhagic kidneys, enlarged congested spleen and pancreas, etc. were found on postmortem examination. FAdVs were detected in 90% of the flocks except commercial layer flock from Dinajpur. Three serotypes, namely, 8b (70%), 11 (10%), and 5 (10%) were detected. Anti-FAdV antibody was detected in 80% flocks at the beginning of infection and in 90% of the flocks after recovery from infection. The antibody titer increases significantly (p < 0.05) after recovery from infection. Phylogenetic analysis revealed that the Bangladeshi FAdVs have close identity with viruses from Asia, Europe, and South and North America.ConclusionsThese findings suggested that several introductions of FAdVs were taken place in Bangladesh. To combat the disease, vaccination along with maintenance of biosecurity is essential.

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Identification of chicken CAR homology as a cellular receptor for the emerging highly pathogenic fowl adenovirus 4 via unique binding mechanism.

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