Glycoprotein C of equine herpesvirus 4 plays a role in viral binding to cell surface heparan sulfate.
Abstract: Heparan sulfate moieties of cell surface proteoglycans serve as receptors for several herpesviruses. For herpes simplex virus 1, pseudorabies virus and equine herpesvirus 1, glycoprotein C (gC) homologues have been shown to mediate the binding to cell surface heparan sulfate. However, the role of gC in equine herpesvirus 4 (EHV-4) infection has not yet been analyzed. Using pull-down assay, we first determined that EHV-4 gC as well as gB are heparin-binding glycoproteins. To study the role of gC in EHV-4 infection, we constructed a gC-deletion mutant, WA79DeltagC, where the kanamycin resistant gene was inserted instead of the open reading frame encoding gC. We found that soluble heparin was capable of blocking both wild-type EHV-4 and WA79DeltagC infection of fetal horse kidney. Furthermore, pretreatment of cells with heparinase reduces considerably the ability of both viruses to adsorb to these cells and to form plaques. Similar results were obtained when cellular glycosaminoglycan synthesis was inhibited by chlorate treatment. In addition, we did find that gC protects EHV-4 from complement-mediated neutralization. These results suggest that, like other herpesviruses, EHV-4 gC plays a role in the interaction of the virus with cellular heparan sulfate. Moreover, gC can protect the virus from complement-mediated neutralization.
Publication Date: 2010-03-15 PubMed ID: 20236610DOI: 10.1016/j.virusres.2010.03.003Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study explores the role of glycoprotein C (gC) in Equine Herpesvirus 4 (EHV-4) binding to cell surface heparan sulfate, and its protective function against complement-mediated neutralization. The findings reveal that gC is essential for EHV-4 to effectively interact with cellular heparin sulfate, contributing to the infection process, and it additionally protects the virus from being neutralized by the immune system’s complement system.
Key Information
- Heparan sulfate, found on cell surfaces, serves as a receptor for several herpesviruses, allowing these viruses to bind and invade cells.
- This research focuses on EHV-4, a particular herpesvirus affecting horses, and a glycoprotein called gC which has been seen in other herpesviruses to mediate binding to cellular heparan sulfate.
Research Methods
- The researchers conducted a pull-down assay to determine if gC and another glycoprotein, gB, in EHV-4 are heparin-binding glycoproteins.
- They then created a gC-deletion mutation of the EHV-4 virus, called WA79DeltagC, replacing the gC encoding gene with a kanamycin resistant gene.
- They tested the ability of both the wild-type EHV-4 and WA79DeltagC to infect fetal horse kidneys, in the presence of soluble heparin, and following treatment of the cells with heparinase.
Findings
- Both the wild-type EHV-4 and the gC-deleted virus could bind to and infect horse kidney cells, although their ability to do so was greatly reduced when the cells were pre-treated with heparinase or the glycosaminoglycan synthesis was inhibited by chlorate.
- The researchers found that in addition to aiding the binding process, gC also shields the virus from complement-mediated neutralization, a mechanism through which the immune system deactivates pathogens.
Implications
- This study indicates gC has crucial roles in EHV-4 infection, acting both as a facilitator for binding and takeover of host cells, and as a defender against the immune system’s neutralizing mechanisms.
- With more knowledge on how the EHV-4 virus operates, these findings could provide a basis for developing treatments or preventive strategies for equine herpesvirus and potentially other herpesvirus infections.
Cite This Article
APA
Azab W, Tsujimura K, Maeda K, Kobayashi K, Mohamed YM, Kato K, Matsumura T, Akashi H.
(2010).
Glycoprotein C of equine herpesvirus 4 plays a role in viral binding to cell surface heparan sulfate.
Virus Res, 151(1), 1-9.
https://doi.org/10.1016/j.virusres.2010.03.003 Publication
Researcher Affiliations
- Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
MeSH Terms
- Animals
- Cell Wall / metabolism
- Cell Wall / virology
- Heparitin Sulfate / metabolism
- Herpesvirus 4, Equid / genetics
- Herpesvirus 4, Equid / metabolism
- Horses
- Humans
- Kidney / metabolism
- Kidney / virology
- Sequence Deletion
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / metabolism
- Virus Attachment
Citations
This article has been cited 11 times.- Kremling V, Loll B, Pach S, Dahmani I, Weise C, Wolber G, Chiantia S, Wahl MC, Osterrieder N, Azab W. Crystal structures of glycoprotein D of equine alphaherpesviruses reveal potential binding sites to the entry receptor MHC-I. Front Microbiol 2023;14:1197120.
- Ruan P, Feng X, Cheng A, Wang M, Zhang W, Wu Y, Yang Q, Tian B, Ou X, Sun D, Zhang S, Mao S, Zhu D, Jia R, Chen S, Liu M, Zhao XX, Huang J, Gao Q, Yu Y, Zhang L, Pan L. Evaluation of safety and immunogenicity of duck-plague virus gC/gE double gene deletion. Front Immunol 2022;13:963009.
- Oladunni FS, Horohov DW, Chambers TM. EHV-1: A Constant Threat to the Horse Industry. Front Microbiol 2019;10:2668.
- Stokol T, Serpa PBS, Zahid MN, Brooks MB. Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation. Front Vet Sci 2016;3:99.
- Spiesschaert B, Goldenbogen B, Taferner S, Schade M, Mahmoud M, Klipp E, Osterrieder N, Azab W. Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model. J Virol 2015 Dec;89(23):11899-908.
- Spiesschaert B, Osterrieder N, Azab W. Comparative analysis of glycoprotein B (gB) of equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) in cellular tropism and cell-to-cell transmission. Viruses 2015 Feb 3;7(2):522-42.
- Sun K, Li X, Jiang J, Cheng A, Wang M, Zhu D, Jia R, Chen S, Zhou Y, Chen X, Wang X. Distribution characteristics of DNA vaccine encoded with glycoprotein C from Anatid herpesvirus 1 with chitosan and liposome as deliver carrier in ducks. Virol J 2013 Mar 16;10:89.
- Azab W, El-Sheikh A. The role of equine herpesvirus type 4 glycoprotein k in virus replication. Viruses 2012 Aug;4(8):1258-63.
- Azab W, Zajic L, Osterrieder N. The role of glycoprotein H of equine herpesviruses 1 and 4 (EHV-1 and EHV-4) in cellular host range and integrin binding. Vet Res 2012 Aug 21;43(1):61.
- Said A, Azab W, Damiani A, Osterrieder N. Equine herpesvirus type 4 UL56 and UL49.5 proteins downregulate cell surface major histocompatibility complex class I expression independently of each other. J Virol 2012 Aug;86(15):8059-71.
- Azab W, Osterrieder N. Glycoproteins D of equine herpesvirus type 1 (EHV-1) and EHV-4 determine cellular tropism independently of integrins. J Virol 2012 Feb;86(4):2031-44.
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