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1.
Poult Sci ; 103(7): 103831, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38833958

RESUMO

The recent emergence of hepatitis-hydropericardium syndrome caused by highly pathogenic fowl adenovirus serotype 4 (FAdV-4) has resulted in significant economic losses to the poultry industry. However, the early innate immune response of immune organs within 24 hpi and the induction of autophagy in vivo after FAdV-4 infection have not been fully elucidated. In this study, 35-day-old specific pathogen-free (SPF) chickens were artificially infected with hypervirulent FAdV-4, which resulted in a mortality rate of up to 90%. The results showed that FAdV-4 infection rapidly triggered the innate immune response in vivo of chickens, with the spleen eliciting a stronger innate immune response than the thymus and bursa. During the early stage of viral infection within 24 hpi, the main receptors TLR3/7/21, MDA5, and cGAS were activated via the NF-κB and TBK1/IRF7-dependent signaling pathways, which up-regulated production of inflammatory cytokines and type I interferons. Additionally, the expression levels of the autophagy-related molecules LC3B, Beclin1, and ATG5 were significantly up-regulated at 24 hpi, while degradation of SQSTM1/p62 was observed, suggesting that FAdV-4 infection elicits a complete autophagy response in the spleen. Besides, the colocalization of Fiber2 and LC3B suggested that FAdV-4 infection induced autophagy which benefits FAdV-4 replication in vivo. This study provides new insights into the immunoregulation signal pathways of the early innate immunity in response to hypervirulent FAdV-4 infection in vivo within 24 hpi and the close relationship between viral replication and autophagy.


Assuntos
Infecções por Adenoviridae , Autofagia , Aviadenovirus , Galinhas , Imunidade Inata , Doenças das Aves Domésticas , Baço , Animais , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/imunologia , Infecções por Adenoviridae/virologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Galinhas/imunologia , Baço/virologia , Baço/imunologia , Aviadenovirus/fisiologia , Aviadenovirus/imunologia , Aviadenovirus/patogenicidade , Organismos Livres de Patógenos Específicos , Sorogrupo , Virulência
2.
Front Cell Infect Microbiol ; 14: 1370414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915924

RESUMO

Fowl adenovirus serotype 4 (FAdV-4) is highly pathogenic to broilers aged 3 to 5 weeks and has caused considerable economic loss in the poultry industry worldwide. FAdV-4 is the causative agent of hydropericardium-hepatitis syndrome (HHS) or hydropericardium syndrome (HPS). The virus targets mainly the liver, and HPS symptoms are observed in infected chickens. This disease was first reported in Pakistan but has now spread worldwide, and over time, various deletions in the FAdV genome and mutations in its major structural proteins have been detected. This review provides detailed information about FAdV-4 genome organization, physiological features, epidemiology, coinfection with other viruses, and host immune suppression. Moreover, we investigated the role and functions of important structural proteins in FAdV-4 pathogenesis. Finally, the potential regulatory effects of FAdV-4 infection on ncRNAs are also discussed.


Assuntos
Infecções por Adenoviridae , Aviadenovirus , Galinhas , Genoma Viral , Doenças das Aves Domésticas , Sorogrupo , Animais , Galinhas/virologia , Doenças das Aves Domésticas/virologia , Aviadenovirus/genética , Aviadenovirus/classificação , Aviadenovirus/patogenicidade , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia , Coinfecção/virologia , Coinfecção/veterinária
3.
Poult Sci ; 103(6): 103725, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603933

RESUMO

Since 2012, there has been a noticeable upward trend in the global incidence of inclusion body hepatitis (IBH) cases, leading to substantial economic losses in the poultry industry. In response to this trend, the current study aimed to investigate the phylogenetic information, genetic mutations, and pathogenicity of the highly pathogenic fowl adenovirus (FAdV) strain HN1472, which was isolated from liver samples obtained from a laying flock affected by IBH. This investigation was carried out using 1-day-old specific pathogen-free (SPF) chickens. Recombination and phylogenetic analyses confirmed that HN1472 is a recombinant strain derived from FAdV-8a and FAdV-8b, and exhibited significant genetic divergence in the hexon, fiber, and ORF19 genes. Notably, the phylogenetic analysis identified recombination events in these regions. Furthermore, animal experiments revealed that HN1472 is a highly pathogenic isolate, causing 80% mortality and manifesting clinical signs of IBH in SPF chickens. Furthermore, the recombinant FAdV serotype 8b (FAdV-8b) was found to be widely distributed in various tissues, with a higher concentration in the livers and gizzard tissue at 3 d postchallenge (dpc). Collectively, these findings contribute to our current understanding of the factors influencing the pathogenicity and genetic diversity of FAdV serotype 8b (FAdV-8b) in China.


Assuntos
Infecções por Adenoviridae , Aviadenovirus , Galinhas , Filogenia , Doenças das Aves Domésticas , Animais , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia , Aviadenovirus/genética , Aviadenovirus/patogenicidade , Aviadenovirus/classificação , Aviadenovirus/fisiologia , Organismos Livres de Patógenos Específicos , Virulência , China/epidemiologia , Hepatite Viral Animal/virologia
4.
Poult Sci ; 103(5): 103642, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537408

RESUMO

Fowl adenovirus serotype 11 (FAdV-11) is one of the primary causative agents of inclusion body hepatitis (IBH), which causes substantial economic losses in the world poultry industry. In this study, we characterized the genome of the fowl adenovirus serotype 11 (FAdV-11) isolate FJSW/2021. The full genome of FJSW/2021 was 44, 154 base pairs (bp) in length and had a similar organization to that of previously reported FAdV-11 isolates. Notably, compared with those of other reported FAdV-11 strains, the preterminal protein (pTP) of FAdV-11 FJSW/2021 has six amino acid (aa) insertions (S-L-R-I-I-C) between 470 and 475 and one aa mutation of L476F; moreover, the tandem repeat (TR) regions of TR1 and TR2 were 33 bp (1 repeat) and 1,080 bp (8 repeats) shorter than those of the Canadian nonpathogenic isolate ON NP2, respectively. The pathogenicity of FJSW/2021 was studied in 10-day-old specific pathogen-free chicken embryos following allantoic cavity inoculation and in 1-day-old, 1-wk-old and 2-wk-old SPF chickens following intramuscular inoculation with 107 TCID50 of the virus. The results showed that FJSW/2021 can induce typical severe IBH in chicks less than 2 wk old. These findings highlighted the genetic differences between the pathogenic and non-pathogenic FAdV-11 isolates. The data will provide guidance for identifying the virulence factors of FAdV-11 strains. The animal challenge model developed in our study will allow precise evaluation of the efficacy of potential FAdV-11 vaccine candidates.


Assuntos
Aviadenovirus , Galinhas , Genoma Viral , Doenças das Aves Domésticas , Sorogrupo , Animais , Doenças das Aves Domésticas/virologia , China , Aviadenovirus/genética , Aviadenovirus/patogenicidade , Virulência , Organismos Livres de Patógenos Específicos , Hepatite Viral Animal/virologia , Embrião de Galinha , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia
5.
Vet Microbiol ; 264: 109302, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34922147

RESUMO

Fowl adenovirus serotype 4 (FAdV-4) is the pathogen causing hepatitis-hydropericardium syndrome (HHS) in broilers. Since June 2015, it has emerged as one of the leading causes of economic losses in the poultry industry in China. Although most studies on FAdV-4 have focused on its pathogenicity to broilers, limited studies have been performed on other natural hosts such as ducks and geese. In this study, we assessed the pathogenicity of FAdV-4 to ducks of different ages through intramuscular injection and found that infected ducks showed severe growth depression. The infected ducks also suffered from extensive organ damage and had histopathological changes in the liver, spleen, and kidney. Although the virus infection caused lymphocyte necrosis of immune organs and the development of the bursa of Fabricius (bursa) was inhibited, the humoral immune response of infected ducks to FAdV-4 remained strong. The infected ducks also had high viral load in tissues and shed virus after the challenge. Overall, our research demonstrates that FAdV-4 can infect ducks and adversely affect the productivity of animals. And the viruses shed by infected ducks can pose a potential risk to the same or other poultry flocks.


Assuntos
Infecções por Adenoviridae , Aviadenovirus , Doenças das Aves Domésticas , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/genética , Aviadenovirus/patogenicidade , Patos , Filogenia , Doenças das Aves Domésticas/virologia , Sorogrupo , Eliminação de Partículas Virais
6.
PLoS One ; 16(12): e0261284, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34914781

RESUMO

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.


Assuntos
Adenovirus A das Aves/genética , Adenovirus A das Aves/patogenicidade , Hepatite Animal/patologia , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/genética , Aviadenovirus/patogenicidade , Galinhas/genética , Galinhas/virologia , Surtos de Doenças/veterinária , Hepatite Animal/virologia , Hepatite Viral Animal/virologia , Corpos de Inclusão/patologia , Corpos de Inclusão/virologia , Fígado/patologia , Marrocos/epidemiologia , Filogenia , Reação em Cadeia da Polimerase , Doenças das Aves Domésticas/virologia , Sorogrupo , Organismos Livres de Patógenos Específicos , Virulência
7.
J Virol ; 95(17): e0060321, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34133902

RESUMO

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.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/patogenicidade , Proteínas do Capsídeo/metabolismo , Galinhas/virologia , Mutação , Doenças das Aves Domésticas/virologia , Proteínas Virais/metabolismo , Infecções por Adenoviridae/virologia , Substituição de Aminoácidos , Animais , Aviadenovirus/classificação , Aviadenovirus/genética , Aviadenovirus/isolamento & purificação , Proteínas do Capsídeo/genética , Proteínas Virais/genética , Virulência
8.
Infect Genet Evol ; 90: 104766, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33581328

RESUMO

In September 2019, a highly prevalent infectious disease caused severe hydropericardium hepatitis syndrome (HHS) in a peacock farm in Central China. The disease showed high mortality of 78.6% in 28-42 day-old peacocks. In this study, one strain of highly pathogenic fowl adenovirus serotype 4 (FAdV-4) was isolated from peacocks and designated as HN19. Molecular characterization of amino acid revealed that HN19 contains the same deletions as the dominate strains in chickens in China recently. Phylogenetic analyses revealed that HN19 showed higher homology with other FAdV-4 strains isolated from China, indicating that HN19 might originate from previously FAdV-4 predecessor in China. Experimental infection of the HN19 strain via intramuscular injection led to 100% mortality rate in 21-day-old specific pathogenic-free (SPF) chickens. To our knowledge, this represents the first report on the prevalence of FAdV-4 in peacocks. These results suggested that the potential risk of cross-species transmission of FAdV-4 from chickens to peacocks, highlighting the need for implementing strict biosecurity measures to avoid the mixing of different bird species.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/classificação , Aviadenovirus/patogenicidade , Galliformes , Derrame Pericárdico/veterinária , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/virologia , Animais , Galinhas , Derrame Pericárdico/virologia , Organismos Livres de Patógenos Específicos , Virulência
9.
J Virol ; 95(6)2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33361420

RESUMO

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.


Assuntos
Infecções por Adenoviridae/metabolismo , Aviadenovirus/patogenicidade , Fígado Gorduroso/metabolismo , Receptores X do Fígado/metabolismo , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/fisiologia , Linhagem Celular Tumoral , Galinhas , Fígado Gorduroso/virologia , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Receptores X do Fígado/genética , Sorogrupo , Transdução de Sinais , Triglicerídeos/metabolismo , Replicação Viral
10.
Avian Dis ; 64(3): 315-323, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33205176

RESUMO

Hydropericardium-hepatitis syndrome, a recently emerged disease of chickens, is caused by some strains of fowl adenovirus serotype 4 (FAdV-4). However, the relationship between the immune response and cytokine expression during FAdV-4 infection is largely unknown. In this study, our data showed that all chickens exhibited typical clinical signs and lesions and that the viral load was significantly increased in both the liver and thymus following FAdV-4 infection. We also found that the appearance of tissue lesions in the liver and thymus was consistent with the viral copy numbers, indicating that virus replication in systemic organs closely correlated with disease progression. In addition, the effects of FAdV-4 infection on the transcription of some avian cytokines were studied in vivo. In general, expression of the proinflammatory cytokines interleukin (IL)-2 and interferon (IFN)-α and IFN-ß in the liver and thymus was strongly upregulated. Interestingly, the expression of IL-2 was the most highly upregulated. Expression of the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor (TGF)-ß1 and TGF-ß2, were also upregulated. Moreover, we investigated both the humoral and cellular immune responses in chickens infected with FAdV-4. Compared to those in the noninfected chickens, the antibody levels in chickens infected with FAdV-4 were significantly increased within 30 days postinfection. In addition, the ratio of CD4+/CD8+ T cells was decreased in FAdV-4-infected chickens. Taken together, these findings increase our understanding of the pathogenesis of FAdV-4 in chickens and provide a foundation for additional pathogenesis studies.


Assuntos
Imunidade Adaptativa , Infecções por Adenoviridae/veterinária , Aviadenovirus/fisiologia , Aviadenovirus/patogenicidade , Galinhas , Imunidade Inata , Doenças das Aves Domésticas/imunologia , Infecções por Adenoviridae/imunologia , Infecções por Adenoviridae/virologia , Animais , Doenças das Aves Domésticas/virologia , Sorogrupo , Organismos Livres de Patógenos Específicos , Virulência
11.
Vet Microbiol ; 251: 108880, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33091795

RESUMO

Hydropericardium hepatitis syndrome (HHS) is a fatal disease caused by fowl adenovirus serotype 4 (FAdV-4). Avian viral arthritis is an infectious disease characterized by movement disorders caused by avian orthoreovirus (ARV). In the early 2019, our epidemiologic survey on poultry diseases in eight commercial broiler farms in China showed that FAdV-4 and ARV have a high coinfection rate, accounting for 63 % of all ARV-positive samples. We designed chicken embryo and animal models to investigate the synergistic pathogenicity of FAdV-4 and ARV. Weakness and inappetence were observed in all specific-pathogen-free (SPF) chickens of the experimental group. FAdV-4 and ARV coinfection caused severe embryonic body and hepatic hemorrhage in SPF chicken embryos. Compared with the singular ARV-infected group, joint swelling was more severe in all coinfected groups. Compared with single virus infection, the coinfection of the two viruses increased the mortality of SPF chicken embryos and chickens. FAdV-4 and ARV coinfection resulted in significantly severe macroscopic and microscopic lesions of the liver, spleen, and kidney of SPF chickens. The detection results of viral load in allantoic fluid, liver, and cloacal swabs indicated that ARV enhanced FAdV-4 replication in SPF chicken embryos and chickens. Cytokine detection showed a significant change in interleukin-1 (IL-1), IL-6, and interferon-α (IFN-α) levels in coinfected groups compared with those in the single-infected groups. Additionally, FAdV-4 and ARV coinfection caused severe damage to the SPF chicken's immune system. In summary, these findings provide insights into the pathology, prevention, and treatment of FAdV-4 and ARV coinfection.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/patogenicidade , Coinfecção/veterinária , Coinfecção/virologia , Orthoreovirus Aviário/patogenicidade , Doenças das Aves Domésticas/virologia , Infecções por Reoviridae/veterinária , Animais , Embrião de Galinha , Galinhas/virologia , China , Citocinas/imunologia , Organismos Livres de Patógenos Específicos , Carga Viral , Virulência
12.
Vet Microbiol ; 244: 108670, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32402334

RESUMO

Inclusion body hepatitis (IBH), hydropericardium syndrome, and gizzard erosion associated with fowl adenovirus (FAdV) infections are reported globally and resulted in significant poultry industry economic losses. In 2018, severe IBH appeared in Pakistan in a 17-week-old layer flock. Subsequently, a FAdV-11 strain (designated as PKFAd18) was isolated from liver samples and identified based on phylogenetic analyses of the serotype-specific L1 region of the capsid hexon gene. There is no complete genome sequence of the Pakistani FAdV-11. This study successfully sequenced the complete genome of PKFAd18. The full genome of PKFAd18 contains 43 840 base pairs (bp) with a G + C content of 53.9 %, which is comparable to other FAdV serotypes. Similar to other FAdV-11 strains, PKFAd18 has only one fiber, while FAdV-1 and FAdV-4 have two fibers. Notably, PKFAd18 showed unique characteristics compared to other FAdV-11 strains. A natural large genomic deletion (1215 bp) appeared in tandem repeat region two, relative to the ON-NP2 strain. Phylogenetic analyses of the PKFAd18 penton gene showed higher homology with FAdV-9, highlighting potential natural recombination between FAdV-11 and FAdV-9. Moreover, the pathogenicity of PKFAd18 studied in specific-pathogen-free chickens showed that PKFAd18 is capable of inducing severe IBH and could be responsible for IBH in Pakistan. Thus, the first complete genome of FAdV-11 in Pakistan was sequenced in this study, which enriches the diversity of knowledge about FAdV-11 and is useful for developing diagnostics and vaccines for IBH induced by FAdV-11 in Pakistan.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/genética , Aviadenovirus/patogenicidade , Genoma Viral , Hepatite Animal/virologia , Corpos de Inclusão Viral , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/classificação , Células Cultivadas , Galinhas/virologia , Hepatite Animal/epidemiologia , Fígado/virologia , Masculino , Paquistão/epidemiologia , Filogenia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/virologia , Análise de Sequência de DNA , Organismos Livres de Patógenos Específicos , Virulência
13.
Viruses ; 12(2)2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085479

RESUMO

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.


Assuntos
Apoptose/genética , Aviadenovirus/genética , Fígado/patologia , Proteínas Estruturais Virais/genética , Animais , Apoptose/efeitos dos fármacos , Aviadenovirus/classificação , Aviadenovirus/patogenicidade , Inibidores de Caspase/farmacologia , Linhagem Celular Transformada , Galinhas , China , Fígado/virologia , Neoplasias Hepáticas , Masculino , Doenças das Aves Domésticas/virologia , Sorogrupo , Fatores de Virulência/genética , Replicação Viral/efeitos dos fármacos
14.
Comp Immunol Microbiol Infect Dis ; 68: 101404, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31874355

RESUMO

Fowl adenovirus (FAdV), as the causative agent of hepatitis-hydropericardium syndrome (HHS), poses a significant threat to the poultry industry in China in recent years. In this study, we investigated the immunopathogenesis of a FAdV-4 strain HN/151025 in 60-day-old chickens. The virus was highly virulent in chickens, with a broader tissue tropism in chickens, causing 60 % mortality. Postmortem findings of dead chickens showed mild HHS and liver degeneration and necrosis. Importantly, FAdV-4 infection induced significant upregulation of genes encoding most toll-like receptors, some cytokines (interleukin-1ß, 2, 6, 8, and 18, and interferon-γ), most of avian ß-defensins, myeloid differentiation primary response protein 88, p38 mitogen-activated protein kinases, and inducible nitric oxide synthase, in tissues of infected chicken, especially in spleen and bursa of Fabricius. There was also a significant positive correlation between FAdV-4 genome load and the mRNA expression levels of most of these factors in specific infected tissues. The results indicated the potential role of these proteins in host immune response against FAdV-4 infection. However, overexpression of these proteins might contribute to tissue damage of FAdV-4 infected chickens, and eventually lead to chicken death.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/patogenicidade , Imunidade Inata , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/imunologia , Animais , Galinhas/imunologia , Galinhas/virologia , China , Citocinas/imunologia , Organismos Livres de Patógenos Específicos , Carga Viral , Tropismo Viral , Virulência
15.
Vet Microbiol ; 238: 108427, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31648724

RESUMO

Outbreaks of fowl adenovirus (FAdV) has resulted in huge economic losses in poultry industry in China since 2015. This study detected the pathogens from diseased chickens and determined that fowl adenovirus serotype 4 (FAdV-4) and co-infection of immunosuppressive pathogens were the causes of the outbreaks. Phylogenetic analysis results indicated that these pandemic strains originated from previously FAdV-4 predecessor in China and had obtain gene mutations that might contribute to enhanced pathogenicity of these strains. Compared with early strains, the pathogenicity of novel FAdV-4 strains significantly increased, which led to systemic infections and injuries to multiple organs in the infected chickens. Our study could provide useful information for understanding of the FAdV-4 and favorable theory basis for clinical prevention and control of the disease.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/classificação , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/prevenção & controle , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/genética , Aviadenovirus/patogenicidade , Galinhas , China , Mutação , Filogenia , Doenças das Aves Domésticas/prevenção & controle , Sorogrupo , Virulência/genética
16.
BMC Vet Res ; 15(1): 373, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660972

RESUMO

BACKGROUND: Fowl adenovirus outbreaks have occurred in China since June 2015. This virus is an emerging infectious disease that causes hydropericardium syndrome and inclusion body hepatitis (HPS-IBH), resulting in significant economic loss to poultry farmers. Five fowl adenovirus (FAdV) strains (HN, AQ, AH726, JS07 and AH712) were isolated from Jiangsu and Anhui provinces. RESULTS: Phylogenetic analysis revealed that the five isolates belonged to species C fowl adenovirus serotype 4. An 11 amino-acid deletion in ORF29, relative to an older viral isolate, JSJ13, was observed for all five strains described here. In chicken experiments, 80-100% birds died after intramuscular inoculation and displayed lesions characteristic of HPS-IBH. The viral DNA copies were further detected by hexon-probe based real-time polymerase chain reaction (PCR) in the chicken samples. The viral loads and cytokine profiles were recorded in all the organs after infections. Despite minor genetic differences, the 5 strains displayed significantly different tissue tropisms and cytokine profiles. CONCLUSIONS: Our data enhance the current understanding some of the factors involved in the pathogenicity and genetic diversity of the FAdV serotype 4 (FAdV-4) in China. Our work provides theoretical support for the prevention and control of HPS-IBH in chickens.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/classificação , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/patogenicidade , Galinhas/virologia , China/epidemiologia , Surtos de Doenças , Filogenia , Doenças das Aves Domésticas/epidemiologia , Virulência
17.
J Zhejiang Univ Sci B ; 20(9): 740-752, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379144

RESUMO

Fowl adenovirus serotype 4 (FAdV-4) strain SD1511 was isolated from chickens with severe inclusion body hepatitis and hydropericardium syndrome in Shandong Province, China. The isolate was cultured in primary chicken embryo kidney cells. A study of pathogenicity indicated that SD1511 readily infected 7-35-d-old chickens by intramuscular injection and intranasal and oral routes, causing 50%-100% mortality. The 35-d-old chickens suffered more severe infection than 7- and 21-d-old chickens with mortality highest in the intramuscular injection group. The serum from surviving chickens showed potent viral neutralizing capability. The complete genome of SD1511 was sequenced and analyzed. The strain was found to belong to the FAdV-4 cluster with more than 99% identity with the virulent FAdV-4 strains isolated in China in recent years except for some distinct variations, including deletions of open reading frame 27 (ORF27), ORF48, and part of ORF19. Our findings suggest that SD1511 might be used as a prototype strain for the study of pathogenesis and vaccine development.


Assuntos
Aviadenovirus/genética , Aviadenovirus/patogenicidade , Rim/virologia , Fígado/virologia , Doenças das Aves Domésticas/virologia , Viroses/veterinária , Animais , Anticorpos Neutralizantes , Linhagem Celular , Embrião de Galinha/virologia , Galinhas/virologia , China , Deleção de Genes , Variação Genética , Genoma , Genoma Viral , Genômica , Rim/embriologia , Fases de Leitura Aberta , Sorogrupo , Carga Viral , Virulência , Viroses/virologia
18.
Vet Microbiol ; 235: 257-264, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383310

RESUMO

Wild birds are known reservoirs of bacterial and viral pathogens, some of which have zoonotic potential. This poses a risk to both avian and human health, since spillover into domestic bird populations may occur. In Victoria, wild-caught cockatoos trapped under licence routinely enter commercial trade. The circovirus Beak and Feather Disease Virus (BFDV), herpesviruses, adenoviruses and Chlamydia psittaci have been identified as significant pathogens of parrots globally, with impacts on both aviculture and the conservation efforts of endangered species. In this study, we describe the results of surveillance for psittacid herpesviruses (PsHVs), psittacine adenovirus (PsAdV), BFDV and C. psittaci in wild cacatuids in Victoria, Australia. Samples were collected from 55 birds of four species, and tested using genus or family-wide polymerase chain reaction methods coupled with sequencing and phylogenetic analyses for detection and identification of known and novel pathogens. There were no clinically observed signs of illness in most of the live birds in this study (96.3%; n = 53). Beak and Feather Disease Virus was detected with a prevalence of 69.6% (95% CI 55.2-80.9). Low prevalences of PsHV (1.81%; 95% CI 0.3-9.6), PsAdV (1.81%; 95% CI 0.3-9.6), and C. psittaci (1.81%; 95% CI 0.3-9.6) was detected. Importantly, a novel avian alphaherpesvirus and a novel avian adenovirus were detected in a little corella (Cacatua sanguinea) co-infected with BFDV and C. psittaci. The presence of multiple potential pathogens detected in a single bird presents an example of the ease with which such infectious agents may enter the pet trade and how novel viruses circulating in wild populations have the potential for transmission into captive birds. Genomic identification of previously undescribed avian viruses is important to further our understanding of their epidemiology, facilitating management of biosecurity aspects of the domestic and international bird trade, and conservation efforts of vulnerable species.


Assuntos
Doenças das Aves/epidemiologia , Papagaios/virologia , Psitacose/veterinária , Viroses/veterinária , Vírus/isolamento & purificação , Alphaherpesvirinae/patogenicidade , Animais , Aviadenovirus/patogenicidade , Doenças das Aves/microbiologia , Doenças das Aves/virologia , Chlamydophila psittaci , Circovirus/patogenicidade , Coinfecção/microbiologia , Coinfecção/veterinária , Coinfecção/virologia , DNA Viral/genética , Espécies em Perigo de Extinção , Papagaios/microbiologia , Prevalência , Psitacose/epidemiologia , Vitória/epidemiologia , Viroses/epidemiologia , Vírus/classificação
19.
Avian Pathol ; 48(5): 477-485, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31155930

RESUMO

Hydropericardium hepatitis syndrome (HHS) is a fatal disease in chickens, mainly caused by fowl adenovirus serotype 4 (FAdV-4). Since June 2015, HHS has appeared in many provinces in China. The disease has spread from broilers to laying hens, breeders and Cherry Valley ducks, seriously endangering the health of the poultry industry in China. In July 2016, an infectious disease was noticed in a goose farm in Jinan, Shandong Province, China, and hydropericardium was the main finding in post mortem investigations. In the actual study, we isolated a FAdV-4 strain from the livers of naturally-infected goslings and designated it as SDJN. We first evaluated its pathogenicity by inoculating Taizhou geese at 10, 20, and 30 days of age with 10-7.15EID50/0.2 ml doses of the SDJN strain in 1 ml allantoic fluid via subcutaneous injection or oral infection. Clinical signs and pericardial effusion appeared in geese infected subcutaneously at 10 days of age, whereas 20- and 30-day-old geese were not susceptible to FAdV-4. The results of real-time PCR showed that the replication ability of FAdV-4 in geese correlated with the age. Furthermore, results from clinical chemistry showed that FAdV-4 damaged the liver and kidney in geese and the results paralleled viral load and gross lesions. Consequently, FAdV-4 was pathogenic in geese, and the pathogenicity was related to age and mode of infection. This study is the first experimental infection of FAdV-4 in geese, which will provide a basis for further understanding of the disease. RESEARCH HIGHLIGHTS Pathogenicity tests with a FAdV-4 were conducted in geese, which included data on clinical signs, gross pathology, histopathology, clinical chemistry and viral load. FAdV-4 could replicate in geese and HHS was successfully induced. Pathogenicity of FAdV-4 in geese was related to the age and routes of infection.


Assuntos
Infecções por Adenoviridae/veterinária , Aviadenovirus/patogenicidade , Gansos/virologia , Doenças das Aves Domésticas/virologia , Infecções por Adenoviridae/patologia , Infecções por Adenoviridae/virologia , Animais , Aviadenovirus/genética , Aviadenovirus/imunologia , China , Feminino , Filogenia , Doenças das Aves Domésticas/patologia , Sorogrupo , Carga Viral/veterinária , Virulência
20.
Infect Genet Evol ; 75: 103928, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31226331

RESUMO

Increasing numbers of hepatitis-hydropericardium syndrome (HHS) outbreaks associated with Fowl adenovirus 4 (FAdV-4) have been confirmed in several provinces of China since 2015, mainly affecting 3-5-week-old broiler chicks, resulting in significant losses to the poultry industry. However, little is currently known regarding the molecular epidemiology and host specificity of FAdV-4 associated with HHS in Southern China. In the present study, we isolated 37 FAdV-4 strains from 52 suspected cases of HHS (33 from broilers, one from a layer, two from ducks, and one from a mandarin duck) from Guangdong province during 2016 to 2017. All 37 FAdV-4 strains obtained showed 100% identity of hexon genes at the nucleotide level, and also showed 100% nucleotide sequence identities with strains obtained from other provinces such as Shandong, Zhejiang, and Anhui, which grouped into a FAdV-C cluster. To our knowledge, this represents the first report of an FAdV-4 strain (GZ1) from a mandarin duck with HHS. Experimental infection of the GZ1 strain via intramuscular injection led to a 100% mortality rate in 21-day-old specific pathogen-free chickens. These data indicate the possibility of the cross-species transmission of FAdV-4, highlighting the need for implementing strict biosecurity measures to avoid the mixing of different bird species.


Assuntos
Aviadenovirus/genética , Galinhas/virologia , Patos/virologia , Genes Virais , Doenças das Aves Domésticas/transmissão , Doenças das Aves Domésticas/virologia , Animais , Aviadenovirus/isolamento & purificação , Aviadenovirus/patogenicidade , China , Filogenia , Especificidade da Espécie , Organismos Livres de Patógenos Específicos
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