Fowl Adenovirus Serotype Research Articles

Pathogenicity of an FAdV-4 isolate to chickens and its genomic analysis.

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.

Pathogenicity of fowl adenovirus (FAdV) serotype 4 strain SDJN in Taizhou geese

ABSTRACTHydropericardium 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 HIGHLIGHTSPathogenicity 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.

Identification, Pathogenicity of Novel Fowl Adenovirus Serotype 4 SDJN0105 in Shandong, China and Immunoprotective Evaluation of the Newly Developed Inactivated Oil-emulsion FAdV-4 Vaccine.

Since mid-2015, numerous outbreaks of hydropericardium-hepatitis syndrome (HHS), which is caused by a novel fowl adenovirus serotype 4 (FAdV-4), have been reported in chickens in parts of China, thereby causing huge economic losses to the poultry industry. Thus, an effective vaccine to control the further spread of infections with this hyper-virulent FAdV-4 is imperative. In this study, we isolated a novel FAdV-4 strain SDJN0105 from a broiler farm with HHS disease in Shandong Province. Pathogenicity was evaluated by the observation of clinical symptoms, necropsy changes, and pathological tissue sections after oral and intramuscular (IM) infection of Specific pathogen free (SPF) chickens. The chickens infected by IM injection all died within three days, and chickens infected via the oculonasal route died within five days post-infection (dpi). Histopathological examination revealed that the pathology was confined to heart, liver, spleen, lung, kidney, and particularly the liver. Irrespective of the inoculation route, the highest viral DNA copy numbers were detected in the livers of infected chickens. The mRNA expression levels of IL-1β, IL-6, IL-8, IFNs, TNF-α, Mx, and OASL were significantly upregulated during the viral infection. In addition, an inactivated oil-emulsion FAdV-4 vaccine was developed. The vaccine could provide full protection for SPF chickens against a lethal dose of the FAdV-4 strain SDJN0105 and a high level of antibodies. These results improve our understanding of the innate immune responses in chickens infected with FAdV-4 and the pathogenesis of FAdV-4 caused by host factors, and the developed FAdV-4 vaccine is promising as a drug candidate for the prevention and reduction of the spread of HHS in poultry in China.

Transcriptome analysis of fowl adenovirus serotype 4 infection in chickens

Fowl adenovirus serotype 4 (FAdV-4) is a causative agent of inclusion body hepatitis and hydropericardium–hepatitis syndrome. These diseases cause considerable economic losses in the global poultry industry and are significant stressors for infected chickens. However, the molecular mechanisms of FAdV-4 pathogenesis are poorly understood. In the present study, we identified differentially expressed genes from the livers of FAdV-4-infected chickens using RNA-seq at 7, 14 and 21 days after FAdV-4 infection. We identified 2395 differentially expressed genes at the three time points. These genes were enriched in variety of biological processes and pathways including PPAR and Notch signaling, cytokine–cytokine receptor interactions and Toll-like receptor signaling pathways. The transcriptional data were validated by quantitative real-time PCR. Our results will assist in the understanding of the molecular pathogenesis of FAdV-4 infection and for developing novel antiviral therapies.

Pathogenicity of a fowl adenovirus serotype 4 isolated from chickens associated with hydropericardium-hepatitis syndrome in China

Hydropericardium-hepatitis syndrome (HHS) is characterized by pericardial effusion and hepatitis and causes huge economic losses in the poultry industry in China. In this study, a strain of fowl adenoviruses (FAdV-4) (GX-1) was isolated from liver samples of diseased chickens with HHS. Phylogenetic analysis based on complete genome gene revealed that GX-1 clustered with the C-type fowl adenovirus and was serotyped as FAdV-4. Pathogenicity testing showed that the GX-1 strain caused 100% mortality in 10-day-old specific pathogen-free chickens at a dose of 104 tissue culture infective doses (TCID50) within 3 d post-infection. A viral dose of 103 TCID50 resulted in a 16% survival rate before day 9 and at 102 TCID50 an 80% rate before day 6. At necropsy, livers from infected chickens were swollen and yellow brown with necrotic foci. The hearts were flabby with amber-colored and jelly-like fluid in the pericardial sacs. The kidneys were swollen and congested. Histologically eosinophilic intranuclear inclusion body could be seen in the hepatic cell. The result of histopathological examination also revealed that heart muscle fibers were fractured with extensive congestion and hemorrhaging. Other tissues like kidney, bursa of Fabricius, thymus, and spleen were observed degeneration and necrosis. Virus-specific antibodies appeared in serum beginning at day 14 and reached statistically significant levels at 21, 28, 35, and 42 dpi (P < 0.001). In conclusion, we identified a highly virulent FAdV-4 virus as causative agent of the HHS outbreak reported here. The FAdV-4 GX-1 strain will be valuable for vaccine evaluation and development to prevent and reduce the spread of HHS in the poultry industry.

Gizzard Erosion Associated with Fowl Adenovirus Infection in Slaughtered Broiler Chickens in Iran.

Gizzard erosions have been noticed in slaughtered broiler chickens during inspection at a processing plant in Iran. The condition was detected in piled gizzards derived from seven commercial broiler farms brought to slaughter on the same day. In total, 48 gizzards with lesions underwent thorough pathologic and virologic investigation. Perforation, roughening, and discoloration of the koilin layer as well as inflammation of the mucosa were observed macroscopically. Histologic examination showed dissociation of and cellular debris in the koilin layer accompanied by a loss and degeneration of glandular epithelium with mild to marked infiltration of inflammatory cells in the mucosa, submucosa, and muscular layer. Fowl adenovirus serotypes 1 (FAdV-1), 11 (FAdV-11), and 8a (FAdV-8a) were found in 13, 12, and 1 gizzard(s), respectively. Therein included were two gizzards that showed mixed infections with FAdV-1 and FAdV-11. Detailed analysis of the hexon gene revealed that the Iranian FAdV-1 isolates could be divided into two subclusters, more closely related to either the European (CELO) or the Asian (Ote) FAdV-1 reference strains. The present study, for the first time, describes not only the appearance of gizzard erosion but also the isolation of FAdV-1 and FAdV-8a from broilers in Iran and offers insights on the epidemiology of FAdV infection in Iranian flocks.

Genetic characterization of fowl adenovirus serotype 4 isolates in Southern China reveals potential cross-species transmission

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.

Prevalence of Fowl Adenovirus Serotype 4 and Co-Infection by Immunosuppressive Viruses in Fowl with Hydropericardium Hepatitis Syndrome in Shandong Province, China.

Fowl adenovirus serotype 4 (FAdV-4) is the pathogenic agent of hydropericardium hepatitis syndrome (HHS) in chickens and ducks, which has caused huge economic losses for the Chinese poultry industry since 2015. In order to objectively determine the prevalence and co-infection status of the virus in Shandong province in China, we analyzed a total of 679 clinical cases of chickens and ducks from 36 farms in the province. The results showed that the FAdV-4 infection rate was 65.2% (443/679), and the rate in breeder ducks was almost two-fold higher than that in breeder chickens (68.57% vs. 34.30%). Notably, co-infection by H9N2 avian influenza virus, infectious bursal disease virus, and/or chicken infectious anemia virus was very common in the 443 FAdV-4-positive cases. Furthermore, phylogenetic analysis of the hexon genes of four Shandong FAdV-4 isolates revealed that these strains clustered into Indian reference strains, indicating that the Shandong FAdV-4 strains might have originated in India. These findings provide the first data on the prevalence and co-infection status of FAdV-4 in Shandong province, which may serve as a foundation for the prevention of FAdV-4 in the field.

Complete genome sequence of fowl adenovirus-8b UPM04217 isolate associated with the inclusion body hepatitis disease in commercial broiler chickens in Malaysia reveals intermediate evolution

The main aim of our study was to explore the genome sequence of the inclusion body hepatitis associated Fowl adenovirus serotype 8b (FAdV-8b) UPM04217 and to study its genomic organisation. The nucleotide sequence of the whole genome of FAdV-8b UPM04217 was determined by using the 454 Pyrosequencing platform and the Sanger sequencing method. The complete genome was found to be 44,059bp long with 57.9% G + C content and shared 97.5% genome identity with the reference FAdV-E genome (HG isolate). Interestingly, the genome analysis using ORF Finder, Glimmer3 and FGENESV predicted a total of 39 open reading frames (ORFs) compared to the FAdV-E HG that possessed 46 ORFs. Fourteen ORFs located within the central genomic region and 16 ORFs located within the left and right ends of the genome were assigned as being the high protein-coding regions. The fusion of the small ORFs at the right end terminal specifically in ORF22 and ORF33 could be the result of gene truncation in the FAdV-E HG. The frame shift mutation in ORF25 and other mutations in ORF13 and ORF17 might have lead to the emergence of genes that could have different functions. Besides, one of the minor capsid components, pVI, in FAdV-8b UPM04217 shared the highest similarity of 93% with that of FAdV-D, while only 47% similarity was found with FAdV-E. From the gene arrangement layout of the FAdV genome, FAdV-8b UPM04217 showed intermediate evolution between the FAdV-E HG and the FAdV-D although it was apparently more similar to the FAdV-E HG.

A loop-mediated isothermal amplification coupling with a lateral flow dipstick for rapid and specific detection of fowl adenovirus serotype-4

Fowl adenovirus serotype-4 (FAdV-4) has been recognized as a predominant threat to the broilers aged from three to five weeks. Hydropericardium syndrome (HPS) is one of its major clinical diseases by FAdV-4 resulting in heavy economic losses. In this study, a loop-mediated isothermal amplification coupling with a lateral flow dipstick (LAMP-LFD) was developed for rapid and specific detection of fowl adenovirus serotype-4. The optimized LAMP-LFD can be completed in 60 min at 65 °C. The minimum detection limits of PCR, real-time PCR, nested PCR and LAMP-LFD are 1 × 104 copies/μl, 1 × 102 copies/μl, 10 copies/μl and 10 copies/μl respectively. Moreover, the specificity of the LAMP-LFD assay is satisfactory and does not produce cross reactions with other species. In field samples, 150 samples were assayed by PCR and LAMP-LFD. They agreed on the diagnosis “positive” in 13% of clinical samples, and they agreed on the diagnosis “negative” in 85% of clinical samples. Their probability of agreement is p0 = 147/150 = 13% + 85% = 98%. LAMP-LFD can potentially be modified and applied as a diagnostic tool for FAdV-4 infection especially in resource-limited areas, such as small breeding farms and basic veterinary labs to offer an affordable diagnostic.

An emerging new fowl adenovirus genotype

In this work, we examined the diversity of fowl adenovirus (FAdV) types occurring in Hungary. From diseased chicken flocks in Eastern Hungary, 29 FAdV strains were isolated between 2011 and 2015. We performed molecular typing of the isolates based on their partial hexon sequences. The results showed that representatives from every FAdV species from A to E are present in Hungary, but compared to the findings from our previous survey, a lower number of different FAdV types were detected. Inclusion body hepatitis was always associated with FAdV-2 or -8b, gizzard erosion was caused in almost every case by FAdV-1. Numerous strains belonging to species FAdV-B were found. The complete genome sequence of a candidate new genotype strain, showing the highest divergence from the reference FAdV-5, was determined using next generation sequencing. In order to provide results compatible with the serology-based type classification, multiple genomic regions, including the major antigenic determinants, of the new isolate (strain 40440-M/2015) were compared to their counterparts in the prototype FAdV-5 (strain 340) from species FAdV-B, at both nucleotide and amino acid sequence levels. In different comparative analyses, the two strains were always found to have larger divergence between each other than any two of the most closely related FAdV serotypes. This new emerging FAdV genotype is already present in Hungary and Austria, though its exact pathological role requires further investigations. The introduction of a novel FAdV (geno)type for the classification of these strains is further supported.

Identification of four serotypes of fowl adenovirus in clinically affected commercial poultry co-infected with chicken infectious anaemia virus in Trinidad and Tobago.

Fowl adenovirus (FAdV), which causes the high-impact diseases such as inclusion body hepatitis and hepatitis-hydropericardium syndrome, is of major concern to the poultry industry internationally. This study was carried out in direct response to mortality rates of up to 75% in commercial broiler flocks in Trinidad, West Indies. Symptoms in 3- to 8-week-old broilers and 13- to 18-week-old pullets pointed to infection with an immunosuppressive viral pathogen. The objectives of the study were to determine whether the infectious agent FAdV, along with other viral pathogens, was responsible for the clinical disease, and to obtain information on the serotypes of FAdV that were infecting the birds. Tissue samples from clinically affected birds from eight different farms were tested for chicken infectious anaemia virus (CIAV) and infectious bursal disease virus (IBDV) by real-time reverse transcription polymerase chain reaction (PCR) and for FAdV by conventional PCR. The birds tested positive for FAdV and CIAV, but negative for IBDV. The gene corresponding to the L1 loop of the hexon protein for FAdV was amplified and sequenced. Phylogenetic analysis of seven FAdV strains inferred that four serotypes were likely to be circulating in the chickens. Well supported genetic relatedness was observed for serotype 8a (97.8%), 8b (97.8%), 9 (95.8%) and 11 (98.8%-99.5%). This is the first published report from Trinidad and Tobago on the presence and circulation of pathogenic FAdV strains, in combination with CIAV, in poultry. The data demonstrate a possible need for the introduction of serotype-specific vaccines against FAdV, as well as vaccines against CIAV, in broilers in the region and emphasize the importance of maintaining high levels of biosecurity on farms to prevent the spread of these potentially devastating viruses between farms.

Mechanism of fowl adenovirus serotype 4-induced heart damage and formation of pericardial effusion

Fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium syndrome (HPS), which is characterized by the accumulation of a clear, straw-colored fluid in the pericardial sac, and high mortality rates. In order to explore the mechanism of FAdV-4-induced cardiac damage, dynamic pathology, apoptosis, and inflammatory reactions were analyzed in vivo. Moreover, we detected viral proliferation, and ultrastructure, inflammation and apoptosis of cardiomyocytes (CM) after FAdV-4 infection in vitro. The results showed that FAdV-4 impaired cardiac integrity and function by causing apoptosis and inflammation in vivo. Flow cytometry showed that CM infected with FAdV-4 did not show apoptosis in vitro. In addition, the mRNA expression of four inflammatory cytokines (interleukin (il)1B, il6, il8, and tumor necrosis factor), and activity of three myocardial enzymes were significantly different between FAdV-4 and control groups. However, in vitro, these indexes showed no significant difference between the groups. These observations collectively indicated that the heart was not the target organ of FAdV-4, and the virus may not directly lead to the occurrence of CM apoptosis and inflammation. To explore the source of pericardial effusion, we measured total protein, albumin, aspartate aminotransferase, creatine kinase isoenzyme, lactate dehydrogenase, potassium, sodium, and chloride ions in serum and pericardial effusion. Pericardial effusion was derived from vascular exudation rather than CM degeneration. Further studies are needed to investigate the exudation mechanism of vascular endothelial cells in FAdV-4 infection then weakened or eliminated pericardial effusion to minimize heart injury and/or restore damaged CM.

Pathogenicity and complete genome sequence of a fowl adenovirus serotype 8b isolate from China.

In this study, we determined and analyzed the complete nucleotide sequence of the genome of a fowl adenovirus isolate SD1356 in China and examined its pathogenicity in specific pathogen-free chick embryos and newly hatched chicks. The full genome of SD1356 was 44,454 nucleotides in length with 58.1% G + C content. Sequence alignment and phylogenetic analysis revealed that strain SD1356 was clustered together belonging to serotype 8b of fowl adenoviruses E species (FAdV-8b). No regions homologous to early regions E1, E3, and E4 of mastadenoviruses were recognized, and being very similar to the typical organization of FAdV-E genomes. All infected embryos died 4-6 d post-inoculation with visible lesions, such as hyperemic, stunting, and clubbed down, etc. Additionally, adenovirus was found in tissues or cloacal swabs of all infected birds and most of the contact uninfected controls, despite lack of clinical signs and pathological changes. Together, our study describes the genomic characteristics of an FAdV-8b strain isolated in China. The reported FAdV-8b strain SD1356 is fetal to chick embryos and possesses horizontal transmission capacity in chickens.

Requirement of Cellular Protein CCT7 for the Replication of Fowl Adenovirus Serotype 4 (FAdV-4) in Leghorn Male Hepatocellular Cells Via Interaction with the Viral Hexon Protein.

Fowl adenovirus serotype 4 (FAdV-4) causes hepatitis-hydropericardium syndrome (HHS), leading to severe economic losses in the poultry industry. Although the pathogenesis of FAdV-4 infection has caused much attention, the underlying molecular mechanisms remain poorly understood. Here, we identified chaperonin containing TCP-1 subunit eta (CCT7) as an interacting partner of the FAdV-4 capsid protein hexon. We found that ectopic expression of CCT7 in leghorn male hepatocellular (LMH) cells enhanced hexon expression in pRK5-flag-hexon transfected cells. On the contrary, knockdown of cellular CCT7 by RNAi markedly reduced hexon expression in FAdV-4-infected cells and suppressed viral replication. These data suggest that CCT7 is required for FAdV-4 replication and may serve as a potential target for controlling FAdV-4 infection.

Penton-dodecahedron of fowl adenovirus serotype 4 as a vaccine candidate for the control of related diseases

In some serotypes of adenovirus (Ad), the penton base and attached trimeric fiber assemble into dodecameric virus-like particles called penton-dodecahedron (Pt-Dd), which can be internalized and used to deliver the vaccine antigens and drugs. Fowl adenovirus serotype 4 (FAdV-4) is an important pathogen, causing seriously economic loss to poultry industry in China and other counties. Pt-Dd particles from FAdV-4 infected cells, as well as in those infected with recombinant human Ad expressing fiber-1, fiber-2, and penton base of FAdV-4, were visualized by transmission electron microscopy. For the first time, we proved that FAdV-4 produced Pt-Dd in infected cells. Pt-Dd can also be assembled by the overexpressed recombinant proteins fiber-1, fiber-2, and penton base. Pt-Dd, as well as the recombinant proteins fiber-1, fiber-2, and penton base, were then used to immunize chickens. The humoral immune response, expression of selected immune molecules and challenge results were used to evaluate the immune efficacy of the vaccine candidates. Pt-Dd induced the highest level of enzyme-linked immunosorbent assay antibodies and significant high levels (p < 0.05) of interferonγ, interleukin-4, and major histocompatibility complex II expression in peripheral blood mononuclear cells at 48 h post-infection. The challenge results showed that Pt-Dd, inactivated FAdV-4 vaccine, and fiber-1 induced the best protection (100%), followed by fiber-2 (80%) and penton base (67%). The present study showed that FAdV-4 -Pt-Dd and recombinant fiber-1 are promising FAdV-4 vaccine candidates and could be used to replace the tissue-sourced inactivated FAdV-4 vaccine.

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First report of fowl adenovirus 8a from commercial broiler chickens in Egypt: molecular characterization and pathogenicity

This study was performed to isolate fowl adenovirus (FAdV) circulating in commercial meat-type chicken in Egypt during 2015 and to identify the pathogenicity of the isolated virus. Cloacal swabs were collected from 9 commercial broiler farms from chickens of 3-5 wk of age in Behira province in Egypt during 2015. FAdV was isolated on chicken embryo liver cells. The virus was identified by conventional polymerase chain reaction targeting a conserved region in the hexon gene. Moreover, phylogenetic analysis of the L1 loop of the hexon gene revealed that the isolated viruses clustered with reference strains belonging to FAdV serotype 8a. This is the first record of FAdV from Egypt on the GenBank. The isolated virus is closely related to strains directly associated with inclusion body hepatitis (IBH) causing considerable economic losses. Pathogenicity study of the virus did not show any mortality, although necropsy and histopathological examination displayed severe hepatitis and degenerative changes in the immune system after 5 d from infection, proving that the virus can cause IBH with intermittent shedding.

Pathogenic, Phylogenetic, and Serological Analysis of Group I Fowl Adenovirus Serotype 4 SDSX Isolated From Shandong, China.

Hydropericardium hepatitis syndrome (HHS) caused by group I fowl adenovirus serotype 4 (FAdV-4) is an acute and infectious disease in fowl, particularly in broilers aged 3–5 weeks. In June 2015, a highly pathogenic disease outbroke in 25–40 day-old ducklings in Shandong province, characterized similar symptom to HHS. In order to determine the pathogenic mechanism of FAdV-4 (SDSX strain) in meat ducks. We divided 90 25-day-old Cherry Valley meat ducks into three groups (oral, subcutaneous, and control; 30 ducks in each group) and infected them with the virus. HHS, inclusion body hepatitis, and enlargement and hemorrhage of the spleen, kidney, lung, thymus, and brain were observed in FAdV-4-infected meat ducks. Histopathological changes were mainly characterized by severe fatty degeneration in the liver, basophilic inclusion bodies in hepatocytes, and vacuolation in the bursa. More importantly, viral DNA could be detected by quantitative real-time polymerase chain reaction in several viscera tissues (e.g., heart, liver, spleen) on the third day after infection. Notably, the livers of the two infected groups contained the highest concentration of viral DNA. In addition, immune responses were studied based on titer levels of the virus antibody and the levels of inflammatory cytokines interleukin (IL)-2 and interferon (IFN)-γ, and most levels were significantly upregulated, indicating that the host immune responses were activated early in infection. These findings increase our understanding of the pathogenicity of FAdV-4 (SDSX) in meat ducks and provide the foundation for further in-depth study of the pathogenic mechanism of this virus.

Inhibition of fowl adenovirus serotype 4 replication in Leghorn male hepatoma cells by SP600125 via blocking JNK MAPK pathway

Fowl Adenoviruses (FAdVs) are widely-distributed pathogens across the globe. Fowl adenovirus serotype 4 (FAdV-4), the causative agent for chicken hydropericardium syndrome (HPS) with a high mortality in the infected flocks, has caused severe economic losses to the poultry industry of China in the past few years. Although vaccination against FAdV-4 has been implemented, the prevention and control of FAdV-4 infection is still not very successful. Here, we report that FAdV-4 markedly inhibits Leghorn male hepatoma (LMH) cell growth and this inhibition could be abolished by a small molecule SP600125, a JNK MAPK specific inhibitor. Furthermore, SP600125 considerably suppressed FAdV-4-induced phosphorylation of p38 and JNK MAPK. Importantly, SP600125 promoted type I interferon production associated with inhibition of FAdV-4 replication. Thus, FAdV-4 might employ the JNK MAPK pathway for the benefit of its replication, and SP600125 may have the potential of being used as an anti-virus drug for the control FAdV-4 infection.