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

2019

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.

Section: Roles Of Host Factors In the Pathogenesis Of Hypervirulenmentioning

confidence: 99%

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

Wang

2019

“…It was reported that FAdV4 induced liver injury through apoptosis, autophagy, and an acute inflammatory response [13]. However, the molecular mechanism underlying FAdV4-induced apoptosis is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…It was found that human adenovirus protein X (PX), also named Mu, modulates expression of E2 proteins [10], and is involved in taking the linear double-stranded DNA genome to the capsid during viral replication [11,12], but the role of Fowl adenovirus PX is largely unknown. A recent report indicates that the FAdV4 isolate caused liver injury largely through apoptosis, autophagy and a severe inflammatory response [13]. However, the pathogenesis of FAdV4 infection is still not clear.…”

Section: Introductionmentioning

confidence: 99%

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

Duan

Wang

et al. 2020

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.

“…FAdV-4 is a hepatotropic virus that causes inclusion body hepatitis and hydropericardium syndrome. It has been reported that FAdV-4 induces liver injury via apoptosis, autophagy, and a severe inflammatory response [29]. Among the organs of FAdV-4 infected chickens, the liver had the highest viral load, followed by the spleen, and a great number of basophilic inclusion bodies were observed in the liver [2,30].…”

Section: Discussionmentioning

confidence: 99%

“…Although FAdV-4-infection causes severe inflammatory response and induces target organ damage [29,30], the underlying mechanism of FAdV-4 infection is largely unknown. In this study, we analyzed the binding partners of FAdV-4 hexon in leghorn male hepatocellular cells by a liquid chromatography-mass spectrograph-based proteomic approach and identified a crucial cellular protein CCT7 associated with the replication of FAdV-4.…”

Section: Introductionmentioning

confidence: 99%

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

Duan

et al. 2019

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.