scholarly journals 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

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 107 ◽  
Author(s):  
Junfeng Gao ◽  
Mingliang Zhao ◽  
Xueyan Duan ◽  
Yongqiang Wang ◽  
Hong Cao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Cellular Protein ◽  
Economic Losses ◽  
Adenovirus Serotype ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Infected Cells ◽  
Lmh Cells ◽  
Fowl Adenovirus Serotype 4

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.

scholarly journals Transcriptome Analysis Reveals the Potential Role of Long Noncoding RNAs in Regulating Fowl Adenovirus Serotype 4-Induced Apoptosis in Leghorn Male Hepatocellular Cells

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1623
Author(s):  
Bo Wen ◽  
Xueping Wang ◽  
Lulu Yang ◽  
Ting Wang ◽  
Xiaolan Hou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Host Cells ◽  
Economic Losses ◽  
Adenovirus Serotype ◽  
Fowl Adenovirus ◽  
Induced Apoptosis ◽  
Lmh Cells ◽  
Fowl Adenovirus Serotype 4

Hepatitis-hydropericardium syndrome (HHS) is caused by fowl adenovirus serotype 4 (FAdV-4) and has resulted in considerable economic losses to the poultry industry globally. FAdV-4 elicits apoptosis in host cells. Long noncoding RNAs (lncRNAs) have emerged as important regulatory RNAs with profound effects on various biological processes, including apoptosis. However, it remains unknown whether lncRNAs participate in FAdV-4-induced apoptosis. In this study, RNA sequencing was applied to determine the transcription of cellular lncRNA in leghorn male hepatocellular (LMH) cells infected with FAdV-4. Cellular RNA transcription analysis demonstrated that FAdV-4 infection elicited 1798 significantly differentially expressed (DE) lncRNAs in infected LMH cells at 24 h post-infection (hpi) compared to mock control infection. In addition, 2873 DE mRNAs were also found. Target prediction and analyses revealed that 775 DE lncRNAs whose 671 target mRNAs were among the DE mRNAs were involved in several signaling pathways, including the AMPK signaling pathway, p53 signaling pathway and insulin signaling pathway. From these 775 DE lncRNAs, we identified 71 DE lncRNAs related to apoptosis based on their target gene functions. Subsequently, lncRNA 54128 was selected from the 71 identified DE lncRNAs, and its role in FAdV-4-induced apoptosis was verified. LncRNA 54128 interference significantly suppressed the rate of apoptosis, which was accompanied by reduced BMP4 transcription levels. To the best of our knowledge, this is the first study to analyze host lncRNA transcription during FAdV-4 infection. Our findings provide a better understanding of host responses to FAdV-4 infection and provide new directions for understanding the potential association between lncRNAs and FAdV-4 pathogenesis.

scholarly journals Metabolomic Profiling Reveals New Insight of Fowl Adenovirus Serotype 4 Infection

2022 ◽  
Vol 12 ◽  
Author(s):  
Haiying Ma ◽  
Yujuan Niu
Keyword(s):  
Host Cell ◽  
High Performance ◽  
Tricarboxylic Acid Cycle ◽  
Amino Sugar ◽  
Host Cells ◽  
Economic Losses ◽  
Adenovirus Serotype ◽  
Fowl Adenovirus ◽  
Lmh Cells ◽  
Fowl Adenovirus Serotype 4

Highly pathogenic fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium syndrome (HPS), which is characterized by pericardial effusion and hepatitis, and is one of the foremost causes of economic losses to the poultry industry over the last 30 years. However, the metabolic changes in cells in response to FAdV-4 infection remain unclear. In order to understand the metabolic interactions between the host cell and virus, we utilized ultra-high-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry to analyze the metabolic profiles with hepatocellular carcinoma cell line (LMH) infected with FAdV-4. The results showed that FAdV-4 could restore metabolic networks in LMH cells and tricarboxylic acid cycle, glycolysis, and metabolism of purines, pyrimidines, alanine, aspartate, glutamate, and amino sugar and nucleotide sugar moieties. Moreover, FAdV-4 production was significantly reduced in LMH cells cultured in glucose or glutamine-deficient medium. These observations highlighted the importance of host cell metabolism in virus replication. Therefore, similarities and disparities in FAdV-4-regulation of the metabolism of host cells could help improve targeted drug and reduce infection.

scholarly journals Identification of a novel immunological epitope on Hexon of fowl adenovirus serotype 4

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jingyi Liu ◽  
Nan Mei ◽  
Yaling Wang ◽  
Xinjin Shi ◽  
Hongjun Chen
Keyword(s):  
Amino Acid Sequence Analysis ◽  
Serum Samples ◽  
Protein Amino Acid ◽  
Adenovirus Serotype ◽  
Linear Peptide ◽  
Hydropericardium Syndrome ◽  
Hexon Protein ◽  
Fowl Adenovirus ◽  
Fowl Adenovirus Serotype 4

AbstractFowl adenovirus serotype 4 (FAdV-4), the causative agent of hepatitis-hydropericardium syndrome (HHS), distributed widely in the poultry farms in China. Hexon is one of the major capsid proteins associated with viral species or serotypes. However, the epitopes of Hexon protein remain largely unknown. In this study, a monoclonal antibody (mAb) specific to Hexon protein of FAdV-4, designated as 3G8, was generated. Subsequently, the linear peptide recognized by 3G8 was mapped and identified as 213AYGAYVK219 using a series of overlapping peptides generated from Hexon protein. Amino acid sequence analysis revealed that the epitope recognized by 3G8 was highly conserved across all the FAdVs. The epitope was immunogenic and could be recognized by FAdV-4 positive chicken serum samples. These findings will enrich our knowledge regarding the epitope on Hexon and provide valuable information for further characterization of the antigenicity of Hexon protein.

scholarly journals Pathogenesis of Hypervirulent Fowl Adenovirus Serotype 4: The Contributions of Viral and Host Factors

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 741 ◽  
Author(s):  
Zeng Wang ◽  
Jun Zhao
Keyword(s):  
Host Defense ◽  
Host Factors ◽  
Present Review ◽  
Defense System ◽  
Adenovirus Serotype ◽  
Vaccine Candidates ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Host Defense System ◽  
Fowl Adenovirus Serotype 4

Since 2015, severe outbreaks of hepatitis-hydropericardium syndrome (HHS), caused by hypervirulent fowl adenovirus serotype 4 (FAdV-4), have emerged in several provinces in China, posing a great threat to poultry industry. So far, factors contributing to the pathogenesis of hypervirulent FAdV-4 have not been fully uncovered. Elucidation of the pathogenesis of FAdV-4 will facilitate the development of effective FAdV-4 vaccine candidates for the control of HHS and vaccine vector. The interaction between pathogen and host defense system determines the pathogenicity of the pathogen. Therefore, the present review highlights the knowledge of both viral and host factors contributing to the pathogenesis of hypervirulent FAdV-4 strains to facilitate the related further studies.

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

2018 ◽  
Author(s):  
Qiuxia Tang ◽  
Ruyi Dangi ◽  
Li Qiu ◽  
Zengqi Yang ◽  
Xinglong Wang
Keyword(s):  
Immune Response ◽  
Recombinant Proteins ◽  
Vaccine Antigen ◽  
Penton Base ◽  
Adenovirus Serotype ◽  
Vaccine Candidates ◽  
Fowl Adenovirus ◽  
Infected Cells ◽  
High Level ◽  
Fowl Adenovirus Serotype 4

AbstractIn some serotypes of adenovirus (Ad), the penton base protein and attached trimeric fiber assemble into dodecameric virus-like particles called penton-dodecahedron (Pt-Dd), which can internalize into cells and can be used to deliver the vaccine antigen and drugs. Fowl adenovirus serotype 4 (FAdV-4) is an important poultry pathogens and causing seriously economic lost to poultry industry in China and several other counties. The produce of Pt-Dd in FAdV-4 infected cells as well as in those infected with the recombinant human Ad expressing fiber-1, fiber-2, and penton base was determine by Transmission electron microscopy (TEM). For the First time, we proved that FAdV-4 produced Pt-Dd in infected cells, which 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, cell mediate immune response (CMI), 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 high levels of CMI, showing a significantly (p < 0.05) high level of interferon γ, interleukin-4, and major histocompatibility complex II expressions in peripheral blood mononuclear cells at 48 h post-infection. The challenge results showed that Pt-Dd, inactivated FAdV-4 vaccine, as well as fiber-1 induced the best protection (100%), followed by fiber-2 (80%) and penton (67%). The present study showed that FAdV-4-Pt-Dd and recombinant fiber-1 are good FAdV-4 vaccine candidates and could be used to replace the tissue-sourced inactivated FAdV-4 vaccine.ImportanceFAdV-4-Pt-Dds were discovered in FAdV-4 infected cells, and which were also assembled in cells transduced with recombinant human adenovirus expressing fiber-1, fiber-2, and penton base. FAdV-4-Pt-Dds internalize into cells with high efficiency, so that it can be used for delivery vaccine antigen or drugs. Immunization chickens with Pt-Dd and fiber-1 obtained by transduction HEK-293T cells induced significant high level humoral and cellular mediated immune responses, and also 100% challenge protection in chickens indicating that they are good FAdV-4 vaccine candidates. What more, the Pt-Dd obtained by transduction HEK-293T cell would have no DNA and adenovirus contamination as adenovirus could not package in HEK-293T cells.

scholarly journals Hydropericardium syndrome caused by fowl adenovirus serotype 4 in replacement pullets

2019 ◽  
Vol 81 (2) ◽  
pp. 245-251 ◽  
Author(s):  
Zhen CHEN ◽  
Shaohua SHI ◽  
Baoming QI ◽  
Su LIN ◽  
Cuiteng CHEN ◽  
...  
Keyword(s):  
Adenovirus Serotype ◽  
Hydropericardium Syndrome ◽  
Fowl Adenovirus ◽  
Fowl Adenovirus Serotype 4

scholarly journals 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

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 627 ◽  
Author(s):  
Kai Meng ◽  
Xiaoyuan Yuan ◽  
Jiang Yu ◽  
Yuxia Zhang ◽  
Wu Ai ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Histopathological Examination ◽  
Lethal Dose ◽  
Economic Losses ◽  
Effective Vaccine ◽  
Drug Candidate ◽  
Adenovirus Serotype ◽  
Oil Emulsion ◽  
Fowl Adenovirus ◽  
Fowl Adenovirus Serotype 4

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.

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