A Novel Role for PX, a Structural Protein of Fowl Adenovirus Serotype 4 (FAdV4), as an Apoptosis-Inducer in Leghorn Male Hepatocellular Cell

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.

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

Viruses ◽

10.3390/v13081623 ◽

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.

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Fowl adenovirus serotype 4-induced apoptosis, autophagy, and a severe inflammatory response in liver

Veterinary Microbiology ◽

10.1016/j.vetmic.2018.07.014 ◽

2018 ◽

Vol 223 ◽

pp. 34-41 ◽

Cited By ~ 9

Author(s):

Yujuan Niu ◽

Qinqin Sun ◽

Guihua Zhang ◽

Xingpo Liu ◽

Yingli Shang ◽

...

Keyword(s):

Inflammatory Response ◽

Adenovirus Serotype ◽

Fowl Adenovirus ◽

Induced Apoptosis ◽

Fowl Adenovirus Serotype 4

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A tandem mass tag-based quantitative proteomic analysis of fowl adenovirus serotype 4-infected LMH cells

Veterinary Microbiology ◽

10.1016/j.vetmic.2021.109026 ◽

2021 ◽

Vol 255 ◽

pp. 109026

Author(s):

Lidan Hou ◽

Xiaochun Chen ◽

Jia Wang ◽

Junping Li ◽

Hanchun Yang

Keyword(s):

Proteomic Analysis ◽

Tandem Mass ◽

Adenovirus Serotype ◽

Quantitative Proteomic Analysis ◽

Fowl Adenovirus ◽

Tandem Mass Tag ◽

Lmh Cells ◽

Fowl Adenovirus Serotype 4 ◽

Mass Tag

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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 ◽

10.3390/v11020107 ◽

2019 ◽

Vol 11 (2) ◽

pp. 107 ◽

Cited By ~ 2

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.

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Metabolomic Profiling Reveals New Insight of Fowl Adenovirus Serotype 4 Infection

Frontiers in Microbiology ◽

10.3389/fmicb.2021.784745 ◽

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.

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