Dataset Information

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.

ABSTRACT: 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.

SUBMITTER: Gao J

PROVIDER: S-EPMC6410038 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

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.

Gao Junfeng J Zhao Mingliang M Duan Xueyan X Wang Yongqiang Y Cao Hong H Li Xiaoqi X Zheng Shijun J SJ

Viruses 20190127 2

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 enhance ...[more]

PMID: 30691230

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Project description:Hepatitis-pericardial syndrome (HHS) is an acute highly infectious avian disease caused by fowl adenovirus serotype 4 (FAdV-4), characterized by fulminant hepatitis and hydropericardium in broilers. Since 2015, a widespread epidemic has occurred in China due to the emergence of hypervirulent FAdV-4 (HPFAdV-4), causing huge losses to the stakeholders. However, the pathogenesis of HPFAdV-4 and the host responses to its infection remain elusive. Here, we show that infection of leghorn male hepatocellular (LMH) cells by HPFAdV-4 induced complete autophagy in cells and that the autophagy induced by recombinant HPFAdV-4-ON1 (rHPFAdV-4-ON1), a viral strain generated by replacing the hexon gene of wild-type HPFAdV-4 (HPFAdV-4-WT) with the one of nonpathogenic strain FAdV-4-ON1, was remarkably mitigated compared to that of the rHPFAdV-4-WT control, suggesting that HPFAdV-4 hexon is responsible for virus-induced autophagy. Importantly, we found that hexon interacted with a cellular protein, BAG3, a host protein that initiates autophagy, and that BAG3 expression increased in cells infected with HPFAdV-4. Furthermore, knockdown of BAG3 by RNA interference (RNAi) significantly inhibited HPFAdV-4- or hexon-induced autophagy and suppressed viral replication. On the contrary, expression of hexon markedly upregulated the expression of BAG3 via activating the P38 signaling pathway, triggering autophagy. Thus, these findings reveal that HPFAdV-4 hexon interacts with the host protein BAG3 and promotes BAG3 expression by activating P38 signaling pathway, thereby inducing autophagy and enhancing viral proliferation, which immensely furthers our understanding of the pathogenesis of HPFAdV-4 infection. IMPORTANCE HHS, mainly caused by HPFAdV-4, has caused large economic losses to the stakeholders in recent years. Infection of leghorn male hepatocellular (LMH) cells by HPFAdV-4 induced complete autophagy that is essential for HPFAdV-4 replication. By a screening strategy, the viral protein hexon was found responsible for virus-induced autophagy in cells. Importantly, hexon was identified as a factor promoting viral replication by interaction with BAG3, an initiator of host cell autophagy. These findings will help us to better understand the host response to HPFAdV-4 infection, providing a novel insight into the pathogenesis of HPFAdV-4 infection.

Dataset Information

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.

Publications

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.

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