scholarly journals The Capsid Protein of Hepatitis E Virus Inhibits Interferon Induction via Its N-Terminal Arginine-Rich Motif

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1050 ◽  
Author(s):  
Shaoli Lin ◽  
Yonglin Yang ◽  
Yuchen Nan ◽  
Zexu Ma ◽  
Liping Yang ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Early Stage ◽  
Case Fatality ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Multifunctional Protein ◽  
Terminal Domain ◽  
Arginine Residues ◽  
Arginine Rich Motif

Hepatitis E virus (HEV) causes predominantly acute and self-limiting hepatitis. However, in HEV-infected pregnant women, the case fatality rate because of fulminant hepatitis can be up to 30%. HEV infection is zoonotic for some genotypes. The HEV genome contains three open reading frames: ORF1 encodes the non-structural polyprotein involved in viral RNA replication; ORF2 encodes the capsid protein; ORF3 encodes a small multifunctional protein. Interferons (IFNs) play a significant role in the early stage of the host antiviral response. In this study, we discovered that the capsid protein antagonizes IFN induction. Mechanistically, the capsid protein blocked the phosphorylation of IFN regulatory factor 3 (IRF3) via interaction with the multiprotein complex consisting of mitochondrial antiviral-signaling protein (MAVS), TANK-binding kinase 1 (TBK1), and IRF3. The N-terminal domain of the capsid protein was found to be responsible for the inhibition of IRF3 activation. Further study showed that the arginine-rich-motif in the N-terminal domain is indispensable for the inhibition as mutations of any of the arginine residues abolished the blockage of IRF3 phosphorylation. These results provide further insight into HEV interference with the host innate immunity.

scholarly journals The fate of Hepatitis E virus capsid protein is regulated by an Arginine-Rich Motif

2021 ◽  
Author(s):  
Kévin Hervouet ◽  
Martin Ferrié ◽  
Maliki Ankavay ◽  
Claire Montpellier ◽  
Charline Camuzet ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Nuclear Translocation ◽  
Hepatitis E ◽  
Particle Assembly ◽  
Humoral Immune ◽  
Antiviral Responses ◽  
Orf2 Protein ◽  
Molecular Determinants ◽  
Arginine Rich Motif

Producing multifunctional proteins is one of the major strategies developed by viruses to condense their genetic information. Here, we investigated the molecular determinants of the multifunctionality of hepatitis E virus (HEV) ORF2 capsid protein. We previously identified 3 isoforms of ORF2 which are partitioned in different subcellular compartments to perform distinct functions. Notably, the infectious ORF2 (ORF2i) protein is the structural component of the virion, whereas the genome-free secreted and glycosylated ORF2 proteins likely act as a humoral immune decoy. We identified a 5 amino acid Arginine-Rich Motif (ARM) located in the ORF2 N-terminal region as a central regulator of the subcellular localizations and functions of ORF2 isoforms. We showed that the ARM controls ORF2 nuclear translocation, promoting regulation of host antiviral responses. This motif also regulates the dual topology and functionality of ORF2 signal peptide, leading to the production of either cytosolic infectious ORF2i or reticular non-infectious glycosylated ORF2 forms. Furthermore, the ARM likely serves as a cleavage site of the glycosylated ORF2 protein. Finally, it promotes ORF2 membrane association that is likely essential for particle assembly. In conclusion, our observations highlight ORF2 ARM as a unique central regulator of ORF2 addressing that finely controls the HEV lifecycle.

scholarly journals Advances in Hepatitis E Virus Biology and Pathogenesis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 267
Author(s):  
Shaoli Lin ◽  
Yan-Jin Zhang
Keyword(s):  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Case Fatality ◽  
Hepatitis E ◽  
Host Cells ◽  
High Rate ◽  
Rapid Progression ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Zoonotic Infections

Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV is a positive-sense single-stranded RNA virus. Human HEV strains mainly belong to four major genotypes in the genus Orthohepevirus A, family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. HEV infection with genotype 1 and 2 mainly presents as acute and self-limiting hepatitis in young adults. However, HEV infection of pregnant women with genotype 1 strains can be exacerbated to fulminant hepatitis, resulting in a high rate of case fatality. As pregnant women maintain the balance of maternal-fetal tolerance and effective immunity against invading pathogens, HEV infection with genotype 1 might dysregulate the balance and cause the adverse outcome. Furthermore, HEV infection with genotype 3 can be chronic in immunocompromised patients, with rapid progression, which has been a challenge since it was reported years ago. The virus has a complex interaction with the host cells in downregulating antiviral factors and recruiting elements to generate a conducive environment of replication. The virus-cell interactions at an early stage might determine the consequence of the infection. In this review, advances in HEV virology, viral life cycle, viral interference with the immune response, and the pathogenesis in pregnant women are discussed, and perspectives on these aspects are presented.

scholarly journals Identification of two neutralization epitopes on the capsid protein of avian hepatitis E virus

2008 ◽  
Vol 89 (2) ◽  
pp. 500-508 ◽  
Author(s):  
E.-M. Zhou ◽  
H. Guo ◽  
F. F. Huang ◽  
Z. F. Sun ◽  
X. J. Meng
Keyword(s):  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Avian Hepatitis E Virus

Production and characterization of a fusion form of hepatitis E virus tORF2 capsid protein in Escherichia coli

2020 ◽  
pp. 1-8
Author(s):  
Mohamed Boumaiza ◽  
Khaled Trabelsi ◽  
Zeineb Choucha ◽  
Ines Akrouti ◽  
Serena Leone ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Hepatitis E

scholarly journals Hepatitis E virus genotype 3 and capsid protein in the blood and urine of immunocompromised patients

2019 ◽  
Vol 78 (3) ◽  
pp. 232-240 ◽  
Author(s):  
Olivier Marion ◽  
Nicolas Capelli ◽  
Sebastien Lhomme ◽  
Martine Dubois ◽  
Mélanie Pucelle ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Immunocompromised Patients ◽  
Genotype 3 ◽  
Virus Genotype

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

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Huixia Li ◽  
Mengnan Fan ◽  
Baoyuan Liu ◽  
Pinpin Ji ◽  
Yiyang Chen ◽  
...  
Keyword(s):  
Viral Infection ◽  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Organic Anion ◽  
Hepatitis E ◽  
Host Cells ◽  
Cell Culture System ◽  
Organic Anion Transporting Polypeptide ◽  
Avian Hepatitis E Virus ◽  
Avian Hev

ABSTRACT 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.

Characterization of monoclonal antibodies to hepatitis E virus (HEV) capsid protein and identification of binding activity

2007 ◽  
Vol 14 (5) ◽  
pp. 555-563 ◽  
Author(s):  
Junkun He ◽  
Robert A. Kuschner ◽  
Vincent Dewar ◽  
Pierre Voet ◽  
Ludmila V. Asher ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Binding Activity

scholarly journals Mapping of linear B cell epitopes on open reading frames 2- and 3-encoded proteins of hepatitis E virus using synthetic peptides

1993 ◽  
Vol 109 (2-3) ◽  
pp. 251-255 ◽  
Author(s):  
Pierre Coursaget ◽  
Yves Buisson ◽  
Nathalie Depril ◽  
Pierre Cann ◽  
Martine Chabaud ◽  
...  
Keyword(s):  
B Cell ◽  
Synthetic Peptides ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
B Cell Epitopes ◽  
Encoded Proteins ◽  
Reading Frames ◽  
Linear B
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