Fowl Aviadenovirus Research Articles

Molecular Epidemiology of Fowl Aviadenoviruses in Broiler Chickens from Vaccinated and Nonvaccinated Breeders.

Fowl aviadenoviruses (FAdVs) are widely distributed among poultry populations, leading to various diseases, immunosuppression, and economic losses. Molecular characterization and phylogenetic analysis of circulating FAdV isolates play a critical role in epidemiologic studies, contributing to the control, monitoring, and prevention of related outbreaks. This study aimed to determine the serotypes of FAdV and reveal the molecular epidemiology in broiler chicken flocks. Samples were taken based on epidemiologically important parameters, such as vaccination status, age, and transmission route. A total of 20 vaccinated flocks (VF, flocks originated from vaccinated breeder lines) and 20 nonvaccinated flocks (NVF, flocks originated from nonvaccinated breeder lines) were randomly selected from flocks reporting suspected FAdV clinical symptoms and deaths. Vaccination was administered by intramuscular injection into the pectoral muscle with a commercial inactivated vaccine at 12 and 18 wk. Liver and cloacal swab samples were collected from each flock over two different production cycles and for three different age groups (1-day-old, 14-day-old, and 28-day-old chickens). The liver and cloacal swap samples were analyzed for FAdV using PCR targeting the hexon loop-1 gene. Molecular detection revealed that 30.0% (24/80) of all flocks were FAdV positive, with 50.0% (20/40) positivity in NVF and 10.0% (4/40) in VF. Sequence analysis of the hexon loop-1 gene revealed that all samples were FAdV-8b serotype (OR670689-OR670712), with 100.0% similarity. One randomly selected FAdV-8b sample was analyzed by whole-genome sequence analysis. This is the first study in Turkey to deposit an FAdV whole-genome sequence (44,139 bp) into the GenBank database (PP236873). Given the significantly lower FAdV positivity rates in VF compared to NVF, the findings indicate that vaccination is an effective tool for protecting against FAdV-related infections.

Fowl Aviadenovirus (FAdV-11) as the causative agent of a vertical outbreak of inclusion body hepatitis in commercial broiler breeders in Brazil

Inclusion body hepatitis (IBH), caused by Fowl Aviadenovirus (FAdV), is a significant disease affecting chickens worldwide. FAdV-11 associated with IBH was identified in 9-day-old commercial broiler breeders in Brazil. The chicks exhibited a sudden increase in daily mortality, accompanied by nonspecific clinical signs, in one house on the farm. The cumulative mortality rate reached 11.13 % by 15 days of age. Macroscopically, the liver was markedly enlarged and pale red with a distinct lobular pattern. Histologically, the liver showed mild to severe multifocal coalescent vacuolar degeneration and necrosis, with hepatocyte nuclei diffusely enlarged and containing large basophilic inclusion bodies. Additionally, the heart exhibited a diffuse, moderate infiltration of lymphocytes and plasma cells, with focal thrombosis in the epicardium. FAdV was detected in liver samples using specific primers for the hexon gene (52 K-fw and 52 K-rv) in a polymerase chain reaction (PCR) assay. Sequencing of the hypervariable region of this gene (Hex L1) for phylogenetic analysis revealed FAdV-D species serotype 11. To our knowledge, this is the first report of FAdV-D serotype 11 as the causative agent of a vertical outbreak of inclusion body hepatitis in broiler breeders in Brazil.

First Molecular Detection and Characterization of Fowl Aviadenovirus Serotype 11 from Broiler Chickens in Chile

Fowl aviadenovirus (FAdV) is a member of the Aviadenovirus genus within the Adenoviridae family. FAdVs are divided into five species based on genomic differences: Fowl aviadenovirus A to Fowl aviadenovirus E (FAdV-A to FAdV-E). They are classified into twelve serotypes (FAdV-1 to FAdV-8a and FAdV-8b to FAdV-11) through cross-neutralization tests. FAdVs are mainly associated with hepatitis hydropericardium syndrome (HHS), adenoviral gizzard erosion (AGE), and inclusion body hepatitis (IBH). The serotypes commonly involved in IBH are FAdV-2, FAdV-11, FAdV-8a, and FAdV-8b. IBH causes significant economic losses in the poultry industry, mainly due to high mortality, reduced productivity, and immunosuppression. This is the first case report on IBH in Chile caused—according to post-mortem findings, molecular analysis, sequencing, and phylogenetic analysis—by FAdV-11. Since the serotype had not previously been reported in Chile, continued monitoring of IBH cases is required to determine the serotype of the circulating FAdVs and adapt preventative vaccination programs.

Genomic and Pathologic Characterization of the First FAdV-C Serotype 4 Isolate from Black-Necked Crane.

Fowl adenoviruses (FAdVs) are distributed worldwide in poultry and incriminated as the etiological agents for several health problems in fowls, and are capable of crossing species barriers between domestic and wild fowls. An FAdV strain was, for the first time, isolated from black-necked crane in this study, and was designated as serotype 4 Fowl aviadenovirus C (abbreviated as BNC2021) according to the phylogenetic analysis of its DNA polymerase and hexon gene. The viral genomic sequence analysis demonstrated that the isolate possessed the ORF deletions that are present in FAdV4 strains circulating in poultry fowls in China and the amino acid mutations associated with viral pathogenicity in the hexon and fiber 2 proteins. A viral challenge experiment with mallard ducks demonstrated systemic viral infection and horizontal transmission. BNC2021 induced the typical clinical signs of hepatitis-hydropericardium syndrome (HHS) with swelling and inflammation in multiple organs and showed significant viral replication in all eight organs tested in the virus-inoculated ducks and their contactees at 6 dpi. The findings highlight the importance of surveillance of FAdVs in wild birds.

Recombinant Fowl aviadenovirus E (FAdV-E) penton base vaccination fails to confer protection against inclusion body hepatitis (IBH) in chickens

ABSTRACT Inclusion body hepatitis (IBH) is a metabolic disease affecting chickens, associated with different serotypes of fowl adenovirus (FAdV). Experimentally tested vaccines against IBH include several capsid-based subunit vaccines, but not the penton base protein. In the present study, specific pathogen-free chickens were vaccinated with recombinant penton base expressed from each of two different FAdV serotypes (FAdV-7 and FAdV-8b), followed by challenge with a virulent IBH-causing strain. No protection was observed with either vaccine, possibly due to the low immunogenicity of each protein and their inability to induce neutralizing antibodies in the host.

A multiplex fluorescence-based loop-mediated isothermal amplification assay for identifying chicken parvovirus, chicken infectious anaemia virus, and fowl aviadenovirus serotype 4

ABSTRACT Chicken parvovirus (ChPV), chicken infectious anaemia virus (CIAV) and fowl adenovirus serotype 4 (FAdV-4) are avian viruses that have emerged in recent years and have endangered the global poultry industry, causing great economic loss. In this study, a multiplex fluorescence-based loop-mediated isothermal amplification (mLAMP) assay for detecting ChPV, CIAV and FAdV-4 was developed to simultaneously diagnose single and mixed infections in chickens. Three primer sets and composite probes were designed according to the conserved regions of the NS gene of ChPV, VP1 gene of CIAV and hexon gene of FAdV-4. Each composite probe was labelled with a different fluorophore, which was detached to release the fluorescence signal after amplification. The target viruses were distinguished based on the colour of the mLAMP products. The mLAMP assay was shown to be sensitive, with detection limits of 307 copies of recombinant plasmids containing the ChPV target genes, 749 copies of CIAV and 648 copies of FAdV-4. The assay exhibited good specificity and no cross-reactivity with other symptomatically related avian viruses. When used on field materials, the results of the mLAMP assay were in 100% agreement with those of the previously published PCR assay. The mLAMP assay is rapid, economical, sensitive and specific, and the results of amplification are directly observable by eye. Therefore, the mLAMP assay is a useful tool for the clinical detection of ChPV, CIAV and FAdV-4 and can be applied in rural areas.

Molecular epidemiology analysis of fowl adenovirus detected from apparently healthy birds in eastern China

BackgroundFowl adenovirus is of major concern to the poultry industry worldwidely. In order to monitor the prevalent status of Fowl adenovirus in China, a total of 1920 clinical samples from apparently healthy birds in the 25 sites of poultry flocks, Slaughterhouse and living bird markets from 8 provinces in eastern China were collected and detected by PCR, sequencing, and phylogenetic analysis.ResultsThe epidemiological survey showed that Fowl adenoviruses were detected in living bird markets, and circulating in a variety of fowl species, including chickens, ducks, goose and pigeons. Among the 1920 clinical samples, 166 samples (8.65%) were positive in the fowl adenovirus PCR detection. In this study, totally all the 12 serotypes (serotypes of 1, 2, 3, 4, 5, 6, 7, 8A, 8B, 9, 10 and 11) fowl adenoviruses were detected, the most prevalent serotype was serotype 1. Phylogenetic analysis indicated that 166 FAdVs of 12 serotypes were divided into 5 fowl adenovirus species (Fowl aviadenovirus A, B, C, D, E).ConclusionsIn the epidemiological survey, 8.65% of the clinical samples from apparently healthy birds were positive in the fowl adenovirus PCR detection. Totally all the 12 serotypes fowl adenoviruses were detected in a variety of fowl species, which provided abundant resources for the research of fowl adenoviruses in China. The newly prevalent FAdV serotypes provides valuable information for the development of an effective control strategy for FAdV infections in fowls.

Síndrome da hepatite-hidropericárdio por Aviadenovirus e em reprodutores de corte

ABSTRACT: Fowl aviadenovirus (FAdV) is an important pathogen in the global poultry industry and the etiology of inclusion body hepatitis-hydropericardium syndrome (HHS) in chickens. Since the 1990s, several outbreaks of HHS have occurred in poultry producing areas, including South America. The coinfection of FAdV and chicken anemia virus (CAV) may markedly impact the incidence of HHS. This study describes an outbreak of HHS in coinfection with CAV in industrial broiler breeders and characterizes the FAdV isolate. The three-week-old male broiler breeders had pale bone marrow, enlarged and yellowish liver, splenomegaly, and atrophied thymus; one chicken was also found with hydropericardium. Virus isolation was performed in SPF chicken embryos of liver and thymus. Tissues of the naturally infected chickens and the inoculated embryos were evaluated by PCR and histopathology. All affected chickens and inoculated embryos were positive for FAdV and CAV. The inoculated embryos had enlarged, greenish and hemorrhagic livers, and 30% died within 7 days of inoculation. Phylogenetic analysis of the FAdV isolate hexon gene partial sequence enabled grouping with E species. The E species has recently become a relevant species in several countries. The association of FAdV with CAV in breeders is of further concern due to both being capable of vertical transmission. Within the last decade, a worldwide upsurge of HHS in broiler breeders owing to failed biosecurity has occurred. In this episode, the failure on biosecurity may have enabled challenge with both FAdV and CAV, with pathological synergism. The CAV-impaired adaptive immunity may have benefited the FAdV infection.

Pathogenicity of Avian Adenoviruses Type D and Type E Isolated from Field Cases of Inclusion Body Hepatitis–Hydropericardium syndrome (IBH–HPS) in Broiler chickens in Egypt

In this study, 210 one-day-old commercial broiler chicks were used to investigate the pathogenicity of two types of Avian Adenoviruses (type D and type E) recently isolated from field cases. These chicks were divided into four groups; birds of group 1 (G1) and group 2 (G2) were experimentally inoculated with two local isolates of fowl aviadenovirus FAdV D-2 and FAdV D-11, respectively, while chicks of group 3 (G3) were experimentally inoculated with FAdV-E 8a. All birds of these three groups were experimentally inoculated orally at one-day of age with a dose of 0.5mL (107 TCID50/mL). Birds of group 4 (G4) served as uninoculated blank controls. Clinical signs, gross lesions and histopathological changes were examined at different intervals post inoculation. Birds of all infected groups showed hydropericardium, focal hepatic necrosis and ecchymotic hemorrhage of thigh and breast muscles. Hepatitis, glomerulonephritis, pericarditis, myocarditis and lymphoid depletion in the spleen were the main histopathological observations. Mortality rates of 12, 16 and 6% were observed in chicks of G1, G2 and G3, respectively, indicating that FAdV-D isolates were more virulent than FAdV-E. Hemagglutination inhibition test revealed significant decrease in antibodies titers against inactivated NDV vaccine in birds of the three FAdVs infected groups compared to the chicks of the control group. In Egypt, several studies reported Adenoviruses infections in broilers; however, to our knowledge this is the first study in which the pathogenicity of FAdVs isolates has been reported. It was concluded that FAdV-D 2, FAdV-D 11 and FAdV-E 8a are primary agents, in addition to possibility of these isolates to act as neglectable immunosuppressive agents incriminating to vaccination failure in chickens.

Characterization of fowl aviadenovirus species in backyard flocks in Turkey

Fowl aviadenovirus infections show a worldwide distribution in poultry at all ages and the incidence of the disease is increasing year after year. Most of the studies have been exhibited the situation of the disease in commercial chickens especially in broilers but there is not sufficient data to estimate in backyards. Totally 389 internal organ samples were collected from 56 flocks from suspicious backyard chickens at ages between 10-35 weeks. Samples were tested by PCR method and nucleotide sequences of hexon genes were used for phylogenetic analyses and comparing with other FAdV sequences submitted to GenBank. Of the 389 samples, 23.9% were found FAdV positive and 30.4% (17/56) of the flocks sampled in the study were infected. This is the first study that was carried out in backyards and two species (D and C) and four serotypes (FAdV-8a, FAdV-3, FAdV-4, and FAdV-10) have been discovered for the first time in Turkey. To understand the epidemiology of FAdV in Turkey and to get enough information about species and serotypes further large scale national studies should be carried out to determine the severity of FAdV infections and to plan control strategies.

A retrospective molecular investigation of selected pigeon viruses between 2018-2021 in Turkey.

A recent first detection of pigeon aviadenovirus-1 and pigeon circovirus co-infection associated with Young Pigeon Disease Syndrome (YPDS) in a pigeon flock in Turkey, prompted a study focused on documenting the distribution of Pigeon aviadenovirus (PiAdV-1 and PiAdV-2), Pigeon circovirus (PiCV), Columbid alphaherpesvirus 1 (pigeon herpesvirus (PiHV)) and Fowl aviadenovirus (FAdV) in the country. These viruses were selected as they are associated with severe disease in pigeons across the world. A total of 192 cloacal swabs were collected from young (<1 year old) pigeons from 16 different private pigeon flocks across Turkey, between 2018 and 2021 as part of routine diagnostic sampling. PiCV genetic material was the most frequently detected 4/16 (25%), PiAdV-1 and CoHV-1 DNA were both found in one flock each, while neither PiAdV-2 and FAdV were detected in any of the studied pigeon flocks. PiCV and PiHV genetic material were both detected in the same pigeon flock’s cloacal samples as a co-infection with the identification of PiHV being a first in Turkey.

Isolation and whole-genome sequencing of a novel aviadenovirus from owls in Japan.

Adenoviruses have been reported to infect a variety of birds. Here, we isolated a novel adenovirus from the liver of a dead owl chick (Bengal eagle owl; Bubo bengalensis) at a raptor-breeding facility in Japan and determined the complete genome sequence of the virus. We performed necropsies on the dead owl chicks and found that they had enlarged livers, pericardial edema, and focal necrosis of the liver tissue. Transmission electron microscopy of the liver tissue revealed a virus-like structure, appearing as paracrystalline arrays in the nucleus, and immunohistochemical staining with anti-adenovirus antibodies showed positive reactions in hepatocytes and other cells. Attempts to isolate the virus from homogenized liver tissue of a dead owl chick showed a cytopathic effect on chicken-derived cultured cells after multiple blind passages. Further, we determined the complete genome sequence of this virus and performed phylogenetic analysis, revealing that this adenovirus belongs to the genus Aviadenovirus, forming a cluster with fowl and turkey aviadenoviruses. The amino acid sequence divergence between the DNA polymerase of this virus and its closest known adenovirus relative is approximately 29%, implying that this virus can be assigned to a new species in the genus Aviadenovirus. Based on our data, this novel owl adenovirus is a likely cause of fatal infections in owls, which may threaten wild and captive owl populations. Further, this virus is unique among raptor adenoviruses in that it infects chicken-derived cultured cells, raising the importance of further investigations to evaluate interspecies transmission of this virus.

Species Fowl aviadenovirus B Consists of a Single Serotype despite Genetic Distance of FAdV-5 Isolates.

Fowl adenoviruses (FAdVs) are infectious agents, mainly of chickens, which cause economic losses to the poultry industry. Only a single serotype, namely FAdV-5, constitutes the species Fowl aviadenovirus B (FAdV-B); however, recently, phylogenetic analyses have identified divergent strains of the species, implicating a more complex scenario and possibly a novel serotype. Therefore, field isolates of the species were collected to investigate the contemporary diversification within FAdV-B, including traditional serotyping. Full genomes of fourteen FAdV-B strains were sequenced and four strains, possessing discriminatory mutations in the antigenic domains, were compared using virus cross-neutralization. Essentially, strains with identical antigenic signatures to that of the first described divergent strain were found in the complete new dataset. While chicken antiserum against FAdV-5 reference strain 340 could not neutralize any of the newly isolated viruses, low homologous/heterologous titer ratios were measured reciprocally. Although they argue against a new serotype, our results indicate the emergence of escape variants in FAdV-B. Charge-influencing amino acid substitutions accounted for only a few mutations between the strains; still, these enabled one-way cross-neutralization only. These findings underline the continued merit of the cross-neutralization test as the gold standard for serotyping, complementary to advancing sequence data, and provide a snapshot of the actual diversity and evolution of species FAdV-B.

Recombinantly Expressed Chimeric Fibers Demonstrate Discrete Type-Specific Neutralizing Epitopes in the Fowl Aviadenovirus E (FAdV-E) Fiber, Promoting the Optimization of FAdV Fiber Subunit Vaccines towards Cross-Protection in vivo.

ABSTRACTVaccines against inclusion body hepatitis in chickens are complicated by the involvement of antigenically diverse fowl adenovirus types. Though immunization with fiber protein confers robust protection, type specificity of fiber antibodies is an obstacle for the desired broad coverage. In this study, we utilized information on multiple linear epitopes predicted in the Fowl Aviadenovirus E (FAdV-E) fiber head (knob) to develop chimeric fibers with an exchange between two serotypes’ sequences, each containing proposed epitopes. Two consecutive segments pertaining to amino acid positions 1 to 441 and 442 to 525/523 in the fibers of FAdV-8a and -8b, types of Fowl Aviadenovirus E that cause inclusion body hepatitis, were swapped reciprocally to result in novel chimeras, crecFib-8a/8b and crecFib-8b/8a. crecFib was indistinguishable from monospecific recombinant fibers in its eactivity with different FAdV antisera in Western blotting. However, contrary to the results for monospecific fibers, crecFib induced cross-neutralizing antibodies against both serotypes in chickens. This demonstrates three nonidentical epitopes in the FAdV-E fiber, the conserved epitope detected in Western blotting and at least two epitopes participating in neutralization, being type specific and located opposite residue position 441-442. Furthermore, we supply conformational evidence for a site in the fiber knob with accessibility critical for neutralization. With such an extended neutralization spectrum compared to those of individual fibers, crecFib was anticipated to fulfill and even extend the mechanistic basis of fiber-mediated protection toward bivalent coverage. Accordingly, crecFib, administered as a single-antigen component, protected chickens simultaneously against challenge with FAdV-8a or -8b, demonstrated by up-to-complete resistance to clinical disease, prevention of target organ-related changes, and significant reduction of viral load.IMPORTANCE The control of inclusion body hepatitis, a disease of economic importance for chicken production worldwide, is complicated by an etiology involving multiple divergent fowl adenovirus types. The fiber protein is principally efficacious in inducing neutralizing and protective antibodies in vaccinated chickens; however, it faces limitations due to its intrinsic type specificity for neutralization. In this study, based on an in silico-guided prediction of multiple epitopes in the fowl adenovirus fiber head’s loops, we designed chimeric proteins, swapping N- and C-distal fiber portions, each containing putative epitopes, between divergent types FAdV-8a and -8b. In in vitro and in vivo studies, the chimeric fiber displayed extended properties compared to those of individual monotype-specific fibers, allowing the number, distribution, functionality, and conformational bearings of epitopes of the fowl adenovirus fiber to be characterized in more detail. Importantly, the chimeric fiber induced cross-neutralizing antibodies and protective responses in chickens against infections by both serotypes, promoting the advancement of broadly protective subunit vaccination strategies against FAdV.

Molecular Investigation of Fowl Aviadenovirus in Broiler Flocks in North Sinai Province

Molecular Investigation of Fowl Aviadenovirus in Broiler Flocks in North Sinai Province

Pathogenicity of field strain of fowl aviadenovirus serotype 11 isolated from chickens with inclusion body hepatitis in Morocco.

Outbreaks of inclusion body hepatitis have emerged in Morocco since 2013 and has resulted in significant economic losses to poultry farms. Three isolates of the causative virus, Fowl adenonovirus (FAdV)were characterized from chickens with IBH, but their pathogenicity has never been investigated. In this work, the pathogenicity of an isolate FAdV 11 (MOR300315 strain) was evaluated by inoculating a group of 40 SPF chickens at 3 days of age by oral route. A group of 40 chicks injected with phosphate-buffered saline solution was used as a control group. The infected chickens showed decreased weight gain from 3dpi. Necropsy displayed pallor and enlargement in liver, swelling and slight hemorrhage in kidney and spleen at 6 dpi. Histopathological changes were mainly characterized by severe and extensive hepatic necrosis associated with the presence of basophilic intra-nuclear inclusion bodies within hepatocytes. The FAdV was reisolated in chicken embryo fibroblast cell culture from liver tissue homogenate of infected chicken from 3 to 6 dpi. Viral DNA was detected by PCR in liver, kidney, spleen and cloacal swabs from 3 to 13 dpi. Antibody response against inoculated FAdV was appeared from 9 dpi. These results confirmed that the FAdV 11 strain is pathogenic in chicken. This study is the first experimental infection of FAdV 11 in chicken in Morocco, which increase our understanding of its pathogenicity in chickens and indicate that preventive measures against FAdV infection in poultry farms should be implemented in Morocco.

Isolation, identification and genetic characterization analysis of a fowl aviadenovirus serotype 4 strain from Tianjin, China.

A fowl aviadenovirus serotype 4 (FAdV-4), Y17215-1, was isolated from the liver of chickens with Hydropericardium-hepatitissyndrome(HHS) in a chicken farm of Tianjin, China. Obvious cytopathic effects were observed in the infected chicken liver hepatocellular carcinoma cell line (LMH cells) at 24h post infection (hpi), which consisted of enlarger and rounder shape of cells. The typical and specific green fluorescence was observed by indirect immunofluorescence assay (IFA). Tissue Culture Infectious Dose50 (TCID50) of it measured after five stable passage in LMH cells reached 106.5TCID50/0.1mL. The strain was inoculated through allantoic membrane of 10-day specific pathogen free(SPF) Chick embryos, the thicker allantoic membranes were observed at 120 hpi. 7-day-old SPF chickens were inoculated with the strain via intramuscular (i.m.) or intranasal (i.n.) injection which resulted in 100% mortality of test chickens. Additionally, the sickness and death of cohabitation chickens in the test group were observed which indicated that the virus can infect healthy chickens by horizontal transmission. The sick chickens showed depression, anorexia and diarrhea with green watery feces. Y17215-1-inoculated chickens mainly presented swollen liver with blood spot, and the enhancement of effusion or yellow gel like effusion that were observed in the pericardium through necropsy. Histopathological examination showed focal necrosis of hepatocytes and characteristic eosinophilic inclusion bodies in the cytoplasm. The results showed that the Y17215-1 isolate had high pathogenicity to SPF chickens. The phylogenetic analysis of the major structural proteins including hexon, fiber-1 and fiber-2 revealed that Y17215-1 strain belongs to C species of fowl aviadenovirus of aviadenovirus family, and has high homology with other Chinese strains isolated in recent years, but was distinct from ON1、MX-SHP95、KR5 and other foreign isolates. This study laid a foundation for further study of epidemiological investigation, pathogenic mechanism as well as the diagnosis and control technology of FAdV-4.

Molecular Investigation of Fowl Aviadenovirus in Broiler Flocks in North Sinai Province

Molecular Investigation of Fowl Aviadenovirus in Broiler Flocks in North Sinai Province

Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9.

Major histocompatibility complex class I (MHC-I) molecules play a critical role in the host’s antiviral response by presenting virus-derived antigenic peptides to cytotoxic T lymphocytes (CTLs), enabling the clearance of virus-infected cells. Human adenoviruses evade CTL-mediated cell lysis, in part, by interfering directly with the MHC-I antigen presentation pathway through the expression of E3-19K, which binds both MHC-I and the transporter associated with antigen processing protein and sequestering MHC-I within the endoplasmic reticulum. Fowl adenoviruses have no homologues of E3-19K. Here, we show that representative virus isolates of the species Fowl aviadenovirus C, Fowl aviadenovirus D, and Fowl aviadenovirus E downregulate the cell surface expression of MHC-I in chicken hepatoma cells, resulting in 71%, 11%, and 14% of the baseline expression level, respectively, at 12 h post-infection. Furthermore, this work reports that FAdV-9 downregulates cell surface MHC-I through a minimum of two separate mechanisms—a lysosomal-independent mechanism that requires the presence of the fowl adenovirus early 1 (FE1) transcription unit located within the left terminal genomic region between nts 1 and 6131 and a lysosomal-dependent mechanism that does not require the presence of FE1. These results establish a new functional role for the FE1 transcription unit in immune evasion. These studies provide important new information about the immune evasion of FAdVs and will enhance our understanding of the pathogenesis of inclusion body hepatitis and advance the progress made in next-generation FAdV-based vectors.

Molecular Detection of a Novel Fowl Adenovirus Serotype-4 (FadV-4) from an Outbreak of Hepatitis Hydropericardium Syndrome in Commercial Broiler Chickens in Egypt.

Hepatitis hydropericardium syndrome (HHS) is an acute infectious disease caused by fowl adenovirus serotype-4 (FAdV-4), which mainly affects broilers aged 4-5 wk. During the winter of January 2021, a 32-day-old broiler flock (Cobb-500) suffered from unusually high mortality (15%) in the Alexandria Governorate, Egypt. The chickens showed depression, ruffled feathers, and greenish diarrhea besides the typical pathologic features of suspected HHS involving flabby hearts, accumulation of a straw-colored fluid in the pericardial sacs, and pale, enlarged hemorrhagic and friable livers with necrotic foci. The kidneys exhibited edema with uric acid depositions. Histopathologic examination of bird livers naturally infected with HHS showed multifocal areas of necrosis, vascular changes, and basophilic intranuclear inclusion bodies (INIB) in the hepatocytes. Molecular identification of the causative agent was accomplished by PCR and sequence analysis of the hyper-variable regions of loop 1 of the hexon gene of fowl aviadenovirus. A pathogenic strain of the novel genotype-4 (FAdV-4) was demonstrated, closely similar to the Israeli strain IS/1905/2019, with an identity of 98%. This is the first report to identify FADV-4 in Egypt, prompting further studies to elucidate its epidemiologic role in all poultry sectors and associated economic losses to provide insights to its control and prevention.