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1.
Vet Res ; 55(1): 23, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374082

RESUMEN

According to previous studies, three representative avian adenoviral strains utilize coxsackievirus-adenovirus receptor (CAR) as a receptor and seem to exhibit diverse binding affinities and modes. Thus, further revealing the exact molecular mechanism underlying the interaction between different FAdVs and the attachment receptor CAR is necessary. In this study, we successfully solved the crystal structure of the FAdV-4 fiber1 knob at 1.6 Šresolution. The interaction between the fibre knob and different domains of CAR was verified by confocal microscopy, coimmunoprecipitation and surface plasmon resonance (SPR) analysis. The fibre knobs of the three representative fowl adenoviruses specifically recognized CAR domain 1 (D1), but the recognition of CAR domain 2 (D2) by chicken embryo lethal orphan (CELO) strains was weak. These results provide insights into the differences in adenovirus‒host cell interactions and have important implications for the exploration of viral invasion mechanisms.


Asunto(s)
Aviadenovirus , Adenovirus A Aviar , Embrión de Pollo , Animales , Receptores Virales/química , Receptores Virales/metabolismo , Pollos/metabolismo , Adenovirus A Aviar/metabolismo
2.
Arch Virol ; 169(7): 146, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864914

RESUMEN

Adenoviruses are a diverse group of viruses that can cause a variety of diseases in poultry, including respiratory and gastrointestinal infections. In turkeys (Meleagris gallopavo), adenoviruses commonly cause hemorrhagic enteritis and, rarely, inclusion body hepatitis. In this study, we investigated fowl adenoviruses (FAdVs) circulating in turkeys in Egypt. Following clinical examination of 500 birds, a portion of the hexon gene was amplified from four out of 50 samples from diseased birds (8%), and one amplicon that produced a strong band was selected for sequencing. Molecular and phylogenetic analysis revealed that the virus in that sample belonged to serotype FAdV-8b. Histopathological and immunohistochemical examinations of prepared tissue sections were performed to confirm the pathological findings. Diseased birds exhibited ruffled feathers, low body weight, a crouching posture, and diarrhea. Gross examination revealed petechial hemorrhage on the spleen, swollen pale liver, and congested intestine. Microscopic examination revealed the presence of eosinophilic and basophilic intranuclear inclusion bodies, nuclear pyknosis, and apoptotic bodies in the liver, congestion, hemorrhage, and fibrosis in the lungs, and desquamation of enterocytes. The presence of viral antigens in the liver, lungs, and intestine was confirmed by immunohistochemistry. To our knowledge, this is the first report of the characterization of an outbreak of inclusion body hepatitis in turkeys (hybrid converter breeds) due to FAdV-8b in Egypt. This finding raises an epidemiological alarm, necessitating further studies, including full-genome sequencing, to trace the virus's origin and genetic diversity.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Pavos , Animales , Infecciones por Adenoviridae/veterinaria , Infecciones por Adenoviridae/virología , Infecciones por Adenoviridae/patología , Aviadenovirus/genética , Aviadenovirus/clasificación , Aviadenovirus/aislamiento & purificación , Proteínas de la Cápside/genética , Egipto , Hepatitis Viral Animal/virología , Hepatitis Viral Animal/patología , Cuerpos de Inclusión Viral/virología , Hígado/virología , Hígado/patología , Filogenia , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/patología , Pavos/virología
3.
Avian Pathol ; 53(3): 155-163, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38206316

RESUMEN

RESEARCH HIGHLIGHTS: Samples of suspected FAdV-infected waterfowl from farms in Shandong Province were collected from 2019 to 2022.Single infections with FAdV were less frequent than mixed infections.477 out of 792 samples (60.23%) tested positive for FAdV nucleic acids.Detection rate of FAdV was 65.47% in fattening duck farms, 55.73% in breeder duck farms and 54.55% in fattening geese farms.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Patos , Gansos , Pollos , Infecciones por Adenoviridae/epidemiología , Infecciones por Adenoviridae/veterinaria , Filogenia , Enfermedades de las Aves de Corral/epidemiología , Aviadenovirus/genética , China/epidemiología
4.
BMC Vet Res ; 20(1): 244, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849870

RESUMEN

BACKGROUND: Fowl adenovirus-4 is a causative agent of hydropericardium hepatitis syndrome (HHS) in chickens and has been frequently reported from many countries. Fowl adenoviruses cause severe disease and mortality in broiler and layer breeders in Azerbaijan. Therefore, in this study, pathological lesions and the dissemination of fowl adenovirus-4 into the visceral organs of infected birds were investigated as well as molecular characterisation of detected strains. For this, liver, heart and spleen from 20 necropsied chickens originated from a broiler breeder flock and a layer breeder flock were embeded on the FTA cards and the samples were analysed for adenovirus-DNA by PCR and sequencing. RESULTS: The findings of necropsy in both broiler and layer breeder chickens were similar, and the liver was severely effected showing hepatitis, and the heart with hydropericardium lesions. The kidneys were swollen with haemorrhages and small white foci on the surface of the spleens were noted. Intestinal congestion and ecchymotic hemorrhages were also observed in some birds. Fowl adenovirus-4-DNA was detected by PCR in all collected organs of 20 birds. The sequence analysis revealed that fowl adenovirus-4 present in Azerbaijan and close similarity of the hexon genes of the adenoviruses existing in the Middle East, North America, far east and Indian subcontinent were determined by phylogenetic analysis. However, sequence diversity was detected from the adenovirus strains circulating in Europe, North and South America. CONCLUSIONS: This study indicates the impact of fowl adenovirus-4 on the poultry health and production, and improved disease control and prevention strategies are necessary to reduce the HHS disease in chickens in Azerbaijan.


Asunto(s)
Infecciones por Adenoviridae , Pollos , Filogenia , Enfermedades de las Aves de Corral , Animales , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/epidemiología , Enfermedades de las Aves de Corral/patología , Infecciones por Adenoviridae/veterinaria , Infecciones por Adenoviridae/virología , Infecciones por Adenoviridae/epidemiología , Azerbaiyán/epidemiología , Aviadenovirus/genética , Aviadenovirus/aislamiento & purificación , Aviadenovirus/clasificación , Hepatitis Viral Animal/virología , Hepatitis Viral Animal/patología , Hepatitis Viral Animal/epidemiología , ADN Viral/genética , Hígado/patología , Hígado/virología , Bazo/patología , Bazo/virología
5.
Biologicals ; 85: 101752, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38401400

RESUMEN

Hydropericardium syndrome (HPS), caused by the Fowl adenovirus 4 (FAdV-4) has led to significant financial losses for the poultry industry globally, including Pakistan over the past few years. Conventional serological methods are time consuming, laborious and less sensitive therefore, a rapid and sensitive ELISA kit is required for the reliable detection of FAdV-4 infection. In the current research, fiber proteins (1 &2) of FAdV-4 were successfully expressed in Escherichia coli and purified using metal affinity chromatography. Using these proteins as antigens, an indirect ELISA for detecting FAdV-4 infection was developed. The developed ELISA showed superior performances upon comparison with Serum neutralization test (SNT). This ELISA also showed reliable detection of FAdV specific antibodies in experimentally infected and vaccinated chickens. This assay produced good correlation on the samples collected from the field with SNT and found essential for large scale serology of the FAdV. No cross reactivity was observed in the ELISA following the testing of the serum samples of different other avian pathogens which showed that this ELISA is specific in detecting the FAdV infection. In conclusion, the developed Fiber protein ELISA is highly sensitive and specific in the detecting the FAdV infection and can be utilized for large scale sero-epidemiology of the disease.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Serogrupo , Pollos , Anticuerpos Antivirales , Infecciones por Adenoviridae/diagnóstico , Infecciones por Adenoviridae/veterinaria , Aviadenovirus/genética , Ensayo de Inmunoadsorción Enzimática/métodos
6.
Microb Pathog ; 181: 106208, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37364799

RESUMEN

The adenovirus family of adenoviridae includes mammalian adenoviruses (mastadenoviruses) and avian adenoviruses (avi-adenoviruses), which are known to cause cold or flu and HPS. A wide variety of afflicted birds, including chicken, pigeon, and psittacine species, have been reported to carry aviadenoviruses. Fowl adenovirus, which causes hydropericardium syndrome (FAdV). The disease is highly contagious and quickly spreads from one flock to another and from one farm to another using mechanical and horizontal transmission paths as well as contaminated litter. The drug Dehydroepiandrosterone (DHEA) is reported to have a significant binding affinity against the 7W83 receptors (-7.7 kcal/mol) respectively. The study focuses on the therapeutic methodology development of Adenoviral infection. In order to discover useful combinations of the drugs in practice, molecular docking methods were also used to match fowl adenovirus protein with anti-viral compounds. To further support the docking effects, extensive molecular dynamics simulations were also used.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Melopsittacus , Enfermedades de las Aves de Corral , Psittaciformes , Animales , Simulación del Acoplamiento Molecular , Adenoviridae , Pollos , Infecciones por Adenoviridae/veterinaria , Filogenia , Mamíferos
7.
Arch Virol ; 168(3): 84, 2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36757474

RESUMEN

Virulent fowl adenovirus serotype 4 (FAdV-4) causes hydropericardium syndrome (HPS) with high mortality in chickens, leading to significant economic losses to the poultry industry. The development of an effective vaccine is essential for successful disease control. Here, we produced recombinant fiber-1 protein of FAdV-4, isolated from a Japanese HPS outbreak strain, JP/LVP-1/96, using a baculovirus expression system and evaluated its immunogenicity and protective efficacy. Recombinant fiber-1 protein induced high levels of neutralizing antibodies in immunized chickens, which were maintained for a minimum of 10 weeks. After being challenged with the virulent FAdV-4 strain JP/LVP-1/96, the immunized chickens did not exhibit clinical signs of infection or histopathological changes, there was a significant reduction in the viral load in various organs and total serum proteins, and albumin levels did not decline. These results suggest that the recombinant fiber-1 protein produced in this study can serve as a subunit vaccine to control HPS in chickens.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Adenoviridae , Infecciones por Adenoviridae/prevención & control , Infecciones por Adenoviridae/veterinaria , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Aviadenovirus/genética , Pollos , Proteínas Recombinantes/genética , Serogrupo , Proteínas Virales/metabolismo
8.
Arch Virol ; 168(2): 68, 2023 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-36656447

RESUMEN

We present the complete genome sequence of an aviadenovirus obtained by metagenomics from cloacal swabs taken from a free-living Eurasian scops owl (Otus scops, a small raptor distributed in Europe and several parts of Asia) in China. Thirty protein coding genes were predicted in this 40,239-bp-long genome, which encodes the largest fiber protein among all reported aviadenoviruses. The viral genome sequence is highly divergent, and the encoded proteins have an average of only 55% amino acid sequence identity to those of other adenoviruses. In phylogenetic analysis, the new owl virus grouped with members of the genus Aviadenovirus and formed a common clade with another owl adenovirus reported previously in Japan. This is the second complete genome sequence of an aviadenovirus discovered in owls, and its proteins have an average of 62% amino acid sequence identity to those of the previously reported owl adenovirus. Combining this result with comparative genomic analysis of all aviadenoviruses, we propose that this owl virus and the previously described Japanese owl adenovirus can be assigned to two new species in the genus Aviadenovirus. This study provides new data on the diversity of aviadenoviruses in wild birds.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Estrigiformes , Animales , Adenoviridae/genética , Aviadenovirus/genética , Filogenia , Genoma Viral , Infecciones por Adenoviridae/veterinaria
9.
Virus Genes ; 59(1): 148-157, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36315316

RESUMEN

Fowl adenovirus (FAdV) serotypes are involved in a variety of clinical manifestations in poultry and has resulted in substantial economic loss to the poultry farmers. Despite the endemicity of Inclusion body hepatitis (IBH) in South Asian countries, including India, its etiology is not well studied. In western India, the rural poultry flocks obtained from the vaccinated parents were experiencing disease outbreaks with substantial economic losses due to heavy outbreaks and mortality. Therefore, the study was conducted to decipher the molecular epidemiology of the FAdV from field outbreaks in western India. A total of 37 commercial broiler poultry flocks and 29 village poultry flocks of western India were visited during 2019 to 2021. Out of these, 19.14% flocks showed incidence of IBH during the age of 15 to 35 days. The mortality ranged from 3.3 percent to 55.28 percent. The samples were subjected for amplification of partial hexon gene covering loop 1 and loop 2. The results revealed 48.28% positivity by PCR. The sequence analysis identified 14 isolates as species D serotype 11 with 0.97 to 0.99% divergence and two as species E serotype 8b with 0.99% divergence. The FAdV-11 isolates showed amino acid substitutions D195N, T399A, N417S, and N496H. The amino acids I188 and N195 were conserved in FAdV-11. The molecular clock in Bayesian methods was used to determine most common ancestor. The isolates MH379249 and MH379248 were determined the most recent common ancestor for FAdV-11 and FAdV-8b isolates. The analysis suggested evolution of 10 FAdV-11 strains in 2012, and four FAdV-11 strains and two FAdV-8b strains in 2018.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Hepatitis , Enfermedades de las Aves de Corral , Animales , Serogrupo , Pollos , Teorema de Bayes , Infecciones por Adenoviridae/epidemiología , Infecciones por Adenoviridae/veterinaria , Adenoviridae , Cuerpos de Inclusión , Hepatitis/epidemiología , Brotes de Enfermedades/veterinaria , Filogenia
10.
Avian Pathol ; 52(6): 438-445, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37746729

RESUMEN

The widespread occurrence of fowl adenovirus serotype 4 (FAdV-4)-induced hepatitis-hydropericardium syndrome (HHS) has led to significant economic losses for the poultry industry. A sensitive, accurate, and practical FAdV-4 diagnostic approach is urgently required to limit the incidence of the disease. In the present study, a practical method for detecting FAdV-4 was developed using the CRISPR/Cas13a system and recombinase-aided amplification. The approach was based on 37°C isothermal detection with visible results being achieved. The detection limit of the target gene with this approach was only 101 copies/µl, making it very sensitive and specific. Clinical samples fared well when tested with the Cas13a detection method. For identifying FAdV-4, this novel detection approach was found to be sensitive, specific, and effective.RESEARCH HIGHLIGHTS First study using the CRISPR/Cas13a-based lateral flow detection assay for FAdV-4 detection.The results can be observed by the naked eye.The developed assay could provide an alternative tool for detection of FAdV-4 with minimal equipment.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Infecciones por Adenoviridae/diagnóstico , Infecciones por Adenoviridae/veterinaria , Serogrupo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Pollos , Adenoviridae/genética , Aviadenovirus/genética
11.
Avian Pathol ; 52(2): 128-136, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36622371

RESUMEN

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.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Virus de la Anemia del Pollo , Infecciones por Parvoviridae , Enfermedades de las Aves de Corral , Animales , Adenoviridae , Infecciones por Adenoviridae/diagnóstico , Infecciones por Adenoviridae/veterinaria , Aviadenovirus/genética , Virus de la Anemia del Pollo/genética , Pollos/virología , Filogenia , Enfermedades de las Aves de Corral/diagnóstico , Serogrupo , Infecciones por Parvoviridae/diagnóstico , Infecciones por Parvoviridae/veterinaria
12.
Avian Pathol ; 52(4): 277-282, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37416969

RESUMEN

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.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Hepatitis , Enfermedades de las Aves de Corral , Animales , Pollos , Infecciones por Adenoviridae/prevención & control , Infecciones por Adenoviridae/veterinaria , Vacunas Sintéticas , Cuerpos de Inclusión , Vacunación/veterinaria , Serogrupo
13.
BMC Vet Res ; 19(1): 5, 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36624468

RESUMEN

BACKGROUND: Fowl 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. RESULTS: The 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). CONCLUSIONS: In 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.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Enfermedades de las Aves de Corral/epidemiología , Infecciones por Adenoviridae/epidemiología , Infecciones por Adenoviridae/veterinaria , Epidemiología Molecular , Filogenia , Pollos , Aviadenovirus/genética , China/epidemiología , Serogrupo
14.
Br Poult Sci ; 64(6): 688-696, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37610326

RESUMEN

1. A total of 150-day-old chicks were divided into three groups of 50 birds (G1-G3); G1 and G2 were orally inoculated at 1-day old with 0.5 ml of 107 TCID50/ml FAdV-D serotype 2 (MT386509.1) and FAdV-E serotype 8a (MW847902), respectively, and G3 was blank control group.2. Cell-mediated immune response was evaluated by detection of CD4, CD8 T lymphocytes and the mRNA expression of IL6 and IL8 in the chicken spleen using q-PCR. Additionally, immunopathology was performed at 3, 5 and 7 day post infection (dpi) and weekly until the end of the experiment.3. Results revealed that transcription of inflammatory cytokines (IL6, IL8) was up regulated in the spleen of FAdV type D and type E infected chickens at various time points relative to the control group. A marked decrease in the number of CD4 and CD8 T lymphocytes at 5 and 7 dpi in G1 of chickens infected with FAdV type D. Whereas, in chickens infected with FAdV type E, the CD4 and CD8 T lymphocytes were markedly decreased at 7 dpi.4. In contrast, there were no significant differences in humoral immune responses against NDV vaccine in (G1 and G2) at different intervals post-vaccination compared to the control group. The histopathology of the bursa, thymus, and spleen in the infected groups showed lymphocytolysis with severe reticular cells hyperplasia and lymphoid depletion.5. In conclusion, fowl adenovirus types D and E have an immunosuppressive effect in broilers which may be considered one of the main causes of the continuous co-infections with other viruses reported in the field during the last 10 years.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Pollos , Infecciones por Adenoviridae/veterinaria , Citocinas/genética , Interleucina-6 , Interleucina-8 , Adenoviridae/genética , Linfocitos T CD8-positivos/patología , Aviadenovirus/genética
15.
J Virol ; 95(17): e0060321, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34133902

RESUMEN

Since 2015, severe hydropericardium-hepatitis syndrome (HHS) associated with a novel fowl adenovirus 4 (FAdV-4) has emerged in China, representing a new challenge for the poultry industry. Although various highly pathogenic FAdV-4 strains have been isolated, the virulence factor and the pathogenesis of novel FAdV-4 are unclear. In our previous studies, we reported that a large genomic deletion (1,966 bp) is not related to increased virulence. Here, two recombinant chimeric viruses, rHN20 strain and rFB2 strain, were generated from a highly pathogenic FAdV-4 strain by replacing the hexon or fiber-2 gene of a nonpathogenic FAdV-4, respectively. Both chimeric strains showed similar titers to the wild-type strain in vitro. Notably, rFB2 and the wild-type strain induced 100% mortality, while no mortality or clinical signs appeared in chickens inoculated with rHN20, indicating that hexon, but not fiber-2, determines the novel FAdV-4 virulence. Furthermore, an R188I mutation in the hexon protein identified residue 188 as the key amino acid for the reduced pathogenicity. The rR188I mutant strain was significantly neutralized by chicken serum in vitro and in vivo, whereas the wild-type strain was able to replicate efficiently. Finally, the immunogenicity of the rescued rR188I was investigated. Nonpathogenic rR188I provided full protection against lethal FAdV-4 challenge. Collectively, these findings provide an in-depth understanding of the molecular basis of novel FAdV-4 pathogenicity and present rR188I as a potential live attenuated vaccine candidate or a novel vaccine vector for HHS vaccines. IMPORTANCE HHS associated with a novel FAdV-4 infection in chickens has caused huge economic losses to the poultry industry in China since 2015. The molecular basis for the increased virulence remains largely unknown. Here, we demonstrate that the hexon gene is vital for FAdV-4 pathogenicity. Furthermore, we show that the amino acid residue at position 188 of the hexon protein is responsible for pathogenicity. Importantly, the rR188I mutant strain was neutralized by chicken serum in vitro and in vivo, whereas the wild-type strain was not. Further, the rR188I mutant strain provided complete protection against FAdV-4 challenge. Our results provide a molecular basis of the increased virulence of novel FAdV-4. We propose that the rR188I mutant is a potential live attenuated vaccine against HHS and a new vaccine vector for HHS-combined vaccines.


Asunto(s)
Infecciones por Adenoviridae/veterinaria , Aviadenovirus/patogenicidad , Proteínas de la Cápside/metabolismo , Pollos/virología , Mutación , Enfermedades de las Aves de Corral/virología , Proteínas Virales/metabolismo , Infecciones por Adenoviridae/virología , Sustitución de Aminoácidos , Animales , Aviadenovirus/clasificación , Aviadenovirus/genética , Aviadenovirus/aislamiento & purificación , Proteínas de la Cápside/genética , Proteínas Virales/genética , Virulencia
16.
J Virol ; 95(6)2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33361420

RESUMEN

Fowl adenovirus serotype 4 (FAdV-4) is a hepatotropic virus that causes severe hepatic damage characterized by basophilic intranuclear inclusion bodies, vacuolar degeneration, and multifocal necrosis in hepatocytes. Many aspects of FAdV-4 infection and pathogenesis, however, remain unknown. Here, we found that FAdV-4-induced hepatic injury is accompanied by the accumulation of oil droplets (triglycerides) in the cytoplasm of hepatocytes, a typical indicator of steatosis, in FAdV-4-infected chickens. Significant upregulation of adipose synthesis-related genes, such as liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding protein-1c (SREBP-1c), and significant downregulation of low-density lipoprotein secretion-related genes and lipid oxidation- and lipid decomposition-related genes were observed in the infected chickens. FAdV-4 infection in cultured leghorn male hepatoma (LMH) cells caused similar signs of steatosis, with alterations in various lipogenesis-related genes. We eliminated the effect of LXR-α activation on FAdV-4-induced steatosis and found that treatment with an LXR-α antagonist (SR9243) and RNA interference (small interfering RNA targeting LXR-α [Si-LXR-α]) decreased the number of oil droplets and the accumulation of lipogenic genes, but treatment with an LXR-α agonist (T0901317) increased the number of oil droplets and the accumulation of lipogenic genes in the cells. Additionally, SR9243 treatment or Si-LXR-α transfection led to significant reductions in viral DNA level, protein expression, and virus production, whereas T0901317 treatment caused significant increases in viral DNA level, protein expression, and virus production. However, inhibition of SREBP-1c activity had no significant effect on virus production. Collectively, these results indicated that FAdV-4-induced steatosis involves activation of the LXR-α signaling pathway, which might be a molecular mechanism underlying the hepatic injury associated with FAdV-4 infection.IMPORTANCE Fowl adenovirus serotype 4 (FAdV-4) is an important hepatotropic adenovirus in chicken, but the underlying mechanism of FAdV-4-induced hepatic injury remains unclear. We report here that infection with FAdV-4 induced the accumulation of oil droplets (triglycerides) in the cytoplasm of hepatocytes, a typical indicator of steatosis, in the livers of chickens. FAdV-4-induced steatosis might be caused by a disrupted balance of fat metabolism, as evidenced by differential regulation of various lipase genes. The significant upregulation of liver X receptor-α (LXR-α) prompted us to investigate the interplay between LXR-α activation and FAdV-4-induced steatosis. Treatment with an agonist, an antagonist, or RNA interference targeting LXR-α in cultured leghorn male hepatoma (LMH) cells indicated that FAdV-4-induced steatosis was dependent upon LXR-α activation, which contributed to virus replication. These results provide important mechanistic insights, revealing that FAdV-4 induces hepatic steatosis by activating the LXR-α signaling pathway and highlighting the therapeutic potential of strategies targeting the LXR-α pathway for the treatment of FAdV-4 infection.


Asunto(s)
Infecciones por Adenoviridae/metabolismo , Aviadenovirus/patogenicidad , Hígado Graso/metabolismo , Receptores X del Hígado/metabolismo , Infecciones por Adenoviridae/virología , Animales , Aviadenovirus/fisiología , Línea Celular Tumoral , Pollos , Hígado Graso/virología , Regulación de la Expresión Génica , Hepatocitos/metabolismo , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Hígado/patología , Receptores X del Hígado/genética , Serogrupo , Transducción de Señal , Triglicéridos/metabolismo , Replicación Viral
17.
Microb Pathog ; 173(Pt A): 105835, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36265735

RESUMEN

In the current study, we have evaluated the protective efficacy of the 'insertion domain' which is commonly found in the capsid penton base protein of many adenoviruses. Using the 'insertion domain' of the penton base protein of a representative fowl adenovirus, fowl adenovirus serotype 4 (FAdV-4), we find that the 'insertion domain' can readily be expressed in a soluble form in the bacterial system, and can be purified in sufficient quantities through simple chromatographic methods. We demonstrate that the 'insertion domain', when employed as a subunit vaccine candidate, provides complete protection against hydropericardium syndrome, caused by FAdV-4, in chickens. The data presented here indicate that the protein, adjuvanted with Montanide™ ISA71 VG, provides complete protection in chickens against a lethal FAdV-4 challenge after administration of two doses (100 µg of the protein per dose) two weeks apart (the first dose at the 7th day of life and a booster dose at the age of 21 days). Furthermore, the purified protein can be stored at low temperatures without any observable loss in the protein integrity up to one year, tested so far. Due to the conserved nature of the 'insertion domain' across the penton base protein of fowl adenoviruses, it is suggested that homologous insertion domains could be employed as highly stable and cost-effective subunit vaccine candidates against infections caused by respective fowl adenoviruses.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Animales , Proteínas de la Cápside , Infecciones por Adenoviridae/prevención & control , Infecciones por Adenoviridae/veterinaria , Pollos , Cápside , Aviadenovirus/genética , Adenoviridae/genética , Vacunas de Subunidad , Serogrupo
18.
Vet Res ; 53(1): 75, 2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-36175926

RESUMEN

Fowl adenovirus serotype 4 (FAdV-4) and FAdV-8b are causative agents of hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH), respectively. HHS and IBH co-infections were often reported in clinical, yet there are no commercially available bivalent vaccines for prevention and control of both FAdV-4 and -8b. In the present study, a chimeric FAdV-4 was firstly generated by substituting fiber-1 of FAdV-4 with fiber of FAdV-8b. The chimeric virus, rFAdV-4-fiber/8b, exhibited similar replication ability in vitro and pathogenicity in vivo to the parental wild type FAdV-4. A single dosage of vaccination with the inactivated rFAdV-4-fiber/8b induced high antibody titers against fiber-2 of FAdV-4 and fiber of FAdV-8b and provided full protection against FAdV-4 and -8b challenge. These results demonstrated that fiber of FAdV-8b could replace the role of fiber-1 of FAdV-4 in the process of viral infection, and rFAdV-4-fiber/8b could be used to make a potential bivalent vaccine for the control and prevention of HHS and IBH.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Hepatitis , Enfermedades de las Aves de Corral , Vacunas Virales , Infecciones por Adenoviridae/prevención & control , Infecciones por Adenoviridae/veterinaria , Animales , Pollos , Cuerpos de Inclusión , Serogrupo , Vacunas Combinadas
19.
Arch Virol ; 167(9): 1879-1883, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35729280

RESUMEN

Duck adenovirus 3 (DuAdV-3; strain HB) was isolated and sequenced. The genome of the Muscovy-duck-origin virus contains a 54-bp insertion in pVIII, a 3-bp deletion in the overlap region of 100K, 22K, and 33K, a 42-bp deletion at the junction of ORF64 and ORF67, and a 715-bp deletion in right noncoding region of the genome. Notably, HB has a strikingly shorter right inverted terminal repeat (ITR) of 50 bp, whereas all other DuAdV-3 isolates have a 721-bp ITR. These findings demonstrate that HB is an insertion and deletion mutant of DuAdV-3.


Asunto(s)
Aviadenovirus , Patos , Adenoviridae/genética , Animales , Aviadenovirus/genética , Secuencia de Bases , Secuencias Repetidas Terminales
20.
Arch Virol ; 167(2): 281-292, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34839444

RESUMEN

Hepatitis-hydropericardium syndrome (HHS), caused by fowl adenovirus serotype 4 (FAdV-4), has spread on chicken farms worldwide, causing huge economic losses. Currently, the exact mechanism of pathogenesis of FAdV-4 remains unknown. Despite the severe inflammatory damage observed in chickens infected with pathogenic FAdV-4, few studies have focused on the host immune system-virus interactions and cytokine secretion. Host immunity acts as one of the most robust defense mechanisms against infection by pathogens, and cytokines are important in their elimination. However, excessive inflammatory cytokine secretion could contribute to the pathogenesis of FAdV-4. Understanding of the roles of cytokines produced during FAdV-4 infection is important for the study of pathogenicity and for developing strategies to control FAdV-4. Several previous studies have addressed the immune responses to FAdV-4 infection, but there has not been a systematic review of this work. The present review provides a detailed summary of the current findings on cytokine production induced by FAdV-4 infection to accelerate our understanding of FAdV-4 pathogenesis.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Enfermedades de las Aves de Corral , Adenoviridae , Infecciones por Adenoviridae/veterinaria , Animales , Aviadenovirus/genética , Pollos , Citocinas/genética , Serogrupo
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