Heparan Sulfate Proteoglycans Are Required for Cellular Binding of the Hepatitis E Virus ORF2 Capsid Protein and for Viral Infection
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TLDR
It is demonstrated that cell surface heparan sulfate proteoglycans (HSPGs), specifically syndecans, play a crucial role in the binding of pORF2 to Huh-7 liver cells, indicating that a nonenveloped virus like HEV may have also evolved to use HSPGs as cellular attachment receptors.Abstract:
The hepatitis E virus (HEV), a nonenveloped RNA virus, is the causative agent of hepatitis E. The mode by which HEV attaches to and enters into target cells for productive infection remains unidentified. Open reading frame 2 (ORF2) of HEV encodes its major capsid protein, pORF2, which is likely to have the determinants for virus attachment and entry. Using an ∼56-kDa recombinant pORF2 that can self-assemble as virus-like particles, we demonstrated that cell surface heparan sulfate proteoglycans (HSPGs), specifically syndecans, play a crucial role in the binding of pORF2 to Huh-7 liver cells. Removal of cell surface heparan sulfate by enzymatic (heparinase) or chemical (sodium chlorate) treatment of cells or competition with heparin, heparan sulfate, and their oversulfated derivatives caused a marked reduction in pORF2 binding to the cells. Syndecan-1 is the most abundant proteoglycan present on these cells and, hence, plays a key role in pORF2 binding. Specificity is likely to be dictated by well-defined sulfation patterns on syndecans. We show that pORF2 binds syndecans predominantly via 6-O sulfation, indicating that binding is not entirely due to random electrostatic interactions. Using an in vitro infection system, we also showed a marked reduction in HEV infection of heparinase-treated cells. Our results indicate that, analogous to some enveloped viruses, a nonenveloped virus like HEV may have also evolved to use HSPGs as cellular attachment receptors.read more
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Journal ArticleDOI
Hepatitis E Virus Infection
Nassim Kamar,Nassim Kamar,Harry R. Dalton,Florence Abravanel,Florence Abravanel,Jacques Izopet,Jacques Izopet +6 more
TL;DR: In this comprehensive review, the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries are summarized.
Journal ArticleDOI
Hepatitis E virus infection.
Nassim Kamar,Jacques Izopet,Nicole Pavio,Rakesh Aggarwal,Alain B. Labrique,Heiner Wedemeyer,Harry R. Dalton +6 more
TL;DR: HEV infections can be diagnosed by measuring anti-HEV antibodies, HEV RNA or viral capsid antigen in blood or stool and management of immunocompromised individuals involves lowering the dose of immunosuppressive drugs and/or treatment with the antiviral agent ribavirin.
Journal ArticleDOI
Molecular functions of syndecan-1 in disease.
TL;DR: The key molecular functions of syndecan-1 in modulating the onset, progression, and resolution of inflammatory diseases, cancer, and infection are discussed.
Journal ArticleDOI
Proteoglycans in health and disease: the multiple roles of syndecan shedding.
TL;DR: Recent research into the shedding of syndecan cell‐surface proteoglycans and its physiological relevance are assessed.
Journal ArticleDOI
Pathogenesis and treatment of hepatitis e virus infection.
TL;DR: This review summarizes the current knowledge on the pathogenesis and treatment of HEV infection and explains why it has a more severe course in pregnant women.
References
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Binding of Sindbis Virus to Cell Surface Heparan Sulfate
TL;DR: It is shown here that the widely expressed glycosaminoglycan heparan sulfate can participate in the binding of Sindbis virus to cells, and that a high degree of sulfation was critical for the ability of heparin to bind Sind Bis virus.
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Characterization of growth factor-binding structures in heparin/heparan sulfate using an octasaccharide library.
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The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex.
Elizabeth E. Fry,Susan M. Lea,Terry Jackson,John Newman,Fiona M. Ellard,Wendy Blakemore,Robin Abu-Ghazaleh,A. R. Samuel,Andrew M. Q. King,David I. Stuart +9 more
TL;DR: It is postulate that this site is a conserved feature of FMDVs, such that in the infected animal there is a biological advantage to low affinity, or more selective, interactions with glycosaminoglycan receptors.
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Domain Structure of Heparan Sulfates from Bovine Organs
TL;DR: It is suggested that the formation of iduronic acid residues and their subsequent 2-O-sulfation are coupled within but not outside the contiguous N-Sulfated regions of the heparan sulfate chains and, furthermore, that the 2- and 6-O -sulfotransferase reactions are differentially regulated during heparin sulfate biosynthesis.
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Heparan sulfate glycosaminoglycans are involved in adenovirus type 5 and 2-host cell interactions.
TL;DR: Results demonstrate for the first time that HS-GAGs expressed on the cell surface are involved in the binding of Ad5 and Ad2 to host cells.