Systematic identification of hepatitis E virus ORF2 interactome reveals that TMEM134 engages in ORF2-mediated NF-κB pathway

Tian, Yabin; Huang, Weijin; Yang, Jun J.; Wen, Zhiheng; Yang, Geng; Zhao, Chenyan; Zhang, Heqiu; Wang, Youchun

doi:10.1016/j.virusres.2016.11.027

Cited by 16 publications

(19 citation statements)

References 36 publications

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“…Due to the lack of an efficient cell culture system and animal model, there are few studies about the interaction of HEV with host cells. However, for human HEV, the capsid protein expressed by different systems as the bait protein was used to screen the interaction with host proteins (25,(27)(28)(29). For example, p239, a truncated human HEV capsid protein, can form polymers and was used as the bait protein to research the interactions of HEV with host cells (25,(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

“…However, for human HEV, the capsid protein expressed by different systems as the bait protein was used to screen the interaction with host proteins (25,(27)(28)(29). For example, p239, a truncated human HEV capsid protein, can form polymers and was used as the bait protein to research the interactions of HEV with host cells (25,(27)(28)(29). Following those previous studies about human HEV, ap237 (a truncated capsid protein of CaHEV that corresponds to the amino acid region of human HEV p239) was designed and used as a bait protein to screen the interaction with host proteins from chicken liver cells by a GST pulldown assay in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Next, utilizing p239 as a bait protein, the host factors GRP78/Bip, ␣-tubulin, heat shock protein 90 (HSP90), cytochrome P4502C8, and retinol-binding protein 4 were screened and specifically interacted with the HEV ORF2 protein (25,26). In addition, using another truncated ORF2 protein expressed in insect cells as a bait protein (amino acids 112 to 606), several membrane proteins, such as heparin surface proteoglycans (27), asialoglycoproteins ASGR1 and ASGR2 (28), and transmembrane protein 134 (29), were identified. The functions of these host factors in virus infection are different.…”

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confidence: 99%

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Chicken Organic Anion-Transporting Polypeptide 1A2, a Novel Avian Hepatitis E Virus (HEV) ORF2-Interacting Protein, Is Involved in Avian HEV Infection

Fan

Liu

et al. 2019

J Virol

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Avian hepatitis E virus (HEV) is the main causative agent of big liver and spleen disease in chickens. Due to the absence of a highly effective cell culture system, there are few reports about the interaction between avian HEV and host cells. In this study, organic anion-transporting polypeptide 1A2 (OATP1A2) from chicken liver cells was identified to interact with ap237, a truncated avian HEV capsid protein spanning amino acids 313 to 549, by a glutathione S-transferase (GST) pulldown assay. GST pulldown and indirect enzyme-linked immunosorbent assays (ELISAs) further confirmed that the extracellular domain of OATP1A2 directly binds with ap237. The expression levels of OATP1A2 in host cells are positively correlated with the amounts of ap237 attachment and virus infection. The distribution of OATP1A2 in different tissues is consistent with avian HEV infection in vivo. Finally, when the functions of OATP1A2 in cells are inhibited by its substrates or an inhibitor or blocked by ap237 or anti-OATP1A2 sera, attachment to and infection of host cells by avian HEV are significantly reduced. Collectively, these results displayed for the first time that OATP1A2 interacts with the avian HEV capsid protein and can influence viral infection in host cells. The present study provides new insight to understand the process of avian HEV infection of host cells. IMPORTANCE The process of viral infection is centered around the interaction between the virus and host cells. Due to the lack of a highly effective cell culture system in vitro, there is little understanding about the interaction between avian HEV and its host cells. In this study, a total of seven host proteins were screened in chicken liver cells by a truncated avian HEV capsid protein (ap237) in which the host protein OATP1A2 interacted with ap237. Overexpression of OATP1A2 in the cells can promote ap237 adsorption as well as avian HEV adsorption and infection of the cells. When the function of OATP1A2 in cells was inhibited by substrates or inhibitors, attachment and infection by avian HEV significantly decreased. The distribution of OATP1A2 in different chicken tissues corresponded with that in tissues during avian HEV infection. This is the first finding that OATP1A2 is involved in viral infection of host cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Chicken Organic Anion-Transporting Polypeptide 1A2, a Novel Avian Hepatitis E Virus (HEV) ORF2-Interacting Protein, Is Involved in Avian HEV Infection

Fan

Liu

et al. 2019

J Virol

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“…Intriguingly, the P2 domain has also been reported to block TNFα‐induced NF‐κB signaling via stimulation of TNFα‐induced protein 3 (TNFAIP3, also known as A20), a negative regulator of NF‐κB signaling . In addition, ORF2 protein impedes NF‐κB signaling by preventing IκBα degradation . Thus, HEV has also evolved effective strategies to block TLR‐induced and TNFα‐induced NF‐κB signaling pathway.…”

Section: Innate Immunity Against Hevmentioning

confidence: 99%

“…37 In addition, ORF2 protein impedes NF-κB signaling by preventing IκBα degradation. 38,39 Thus, HEV has also evolved effective strategies to block TLR-induced and TNFα-induced NF-κB signaling pathway.…”

Section: Tnfα and Nf-κb Signaling Pathwaymentioning

confidence: 99%

Immunity against hepatitis E virus infection: Implications for therapy and vaccine development

Hakim

Ikram

Zhou

et al. 2017

Reviews in Medical Virology

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Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide and an emerging cause of chronic infection in immunocompromised patients. As with viral infections in general, immune responses are critical to determine the outcome of HEV infection. Accumulating studies in cell culture, animal models and patients have improved our understanding of HEV immunopathogenesis and informed the development of new antiviral therapies and effective vaccines. In this review, we discuss the recent progress on innate and adaptive immunity in HEV infection, and the implications for the devolopment of effective vaccines and immune-based therapies.

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Hepatitis E in Pregnant Women and the Potential Use of HEV Vaccine to Prevent Maternal Infection and Mortality

et al. 2019

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Purpose of Review Hepatitis E (HEV) is a continuing public health problem in developing countries, causing high mortality in pregnant women. This article reviews the latest knowledge on HEV in pregnancy, the vaccine candidates that have reached clinical trials, and their potential use during pregnancy. Recent Findings New evidence suggests that a genotype-specific tropism to uteroplacental cells contributes to the multifactorial pathology leading to the increased severity of HEV during pregnancy. Data from pregnant women inadvertently vaccinated are limited but show similar rates of adverse events as non-pregnant women, and no evident harm to newborns. Protective anti-HEV IgG antibodies are estimated to last longer after vaccination than natural infection. Accelerated vaccination appears safe and provides protective antibodies similar to a normal dosing regimen. Summary HEV239 is the most extensively studied vaccine and has been shown to be safe and effective, but more data are needed to recommend use of this vaccine on a global basis. Further studies should focus on safety and efficacy in pregnant women, and evaluate a shorter two-dose regime, which is highly warranted in outbreak situations.

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Systematic identification of hepatitis E virus ORF2 interactome reveals that TMEM134 engages in ORF2-mediated NF-κB pathway

Cited by 16 publications

References 36 publications

Chicken Organic Anion-Transporting Polypeptide 1A2, a Novel Avian Hepatitis E Virus (HEV) ORF2-Interacting Protein, Is Involved in Avian HEV Infection

Chicken Organic Anion-Transporting Polypeptide 1A2, a Novel Avian Hepatitis E Virus (HEV) ORF2-Interacting Protein, Is Involved in Avian HEV Infection

Immunity against hepatitis E virus infection: Implications for therapy and vaccine development

Hepatitis E in Pregnant Women and the Potential Use of HEV Vaccine to Prevent Maternal Infection and Mortality

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