Equine herpesvirus 1 entry via endocytosis is facilitated by alphaV integrins and an RSD motif in glycoprotein D.
Abstract: Equine herpesvirus 1 (EHV-1) is a member of the Alphaherpesvirinae, and its broad tissue tropism suggests that EHV-1 may use multiple receptors to initiate virus entry. EHV-1 entry was thought to occur exclusively through fusion at the plasma membrane, but recently entry via the endocytic/phagocytic pathway was reported for Chinese hamster ovary cells (CHO-K1 cells). Here we show that cellular integrins, and more specifically those recognizing RGD motifs such as alphaVbeta5, are important during the early steps of EHV-1 entry via endocytosis in CHO-K1 cells. Moreover, mutational analysis revealed that an RSD motif in the EHV-1 envelope glycoprotein D (gD) is critical for entry via endocytosis. In addition, we show that EHV-1 enters peripheral blood mononuclear cells predominantly via the endocytic pathway, whereas in equine endothelial cells entry occurs mainly via fusion at the plasma membrane. Taken together, the data in this study provide evidence that EHV-1 entry via endocytosis is triggered by the interaction between cellular integrins and the RSD motif present in gD and, moreover, that EHV-1 uses different cellular entry pathways to infect important target cell populations of its natural host.
Publication Date: 2008-09-24 PubMed ID: 18815313PubMed Central: PMC2583640DOI: 10.1128/JVI.00868-08Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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This research article discusses how a protein known as glycoprotein D, found in the Equine herpesvirus 1 (EHV-1), uses a specific combination of cellular integrins and an RSD motif to enter cells via endocytosis. The virus has different entry pathways depending on the cell type it infects.
Understanding the Primary Components
- The research centers around Equine herpesvirus 1 (EHV-1), which is part of the Alphaherpesvirinae family. This virus has a broad tissue tropism, suggesting it can use multiple receptors to start the infection process.
- Evidence up to this point suggested that EHV-1 entry occurs exclusively by fusing with the plasma membrane. However, recent reports showed entry through the endocytic/phagocytic pathway with the involvement of Chinese hamster ovary cells (CHO-K1 cells).
- The study emphasizes the role of cellular integrins, primarily the ones recognizing the RGD motifs like alphaVbeta5. These integrins are vital in the early steps of EHV-1 entry via endocytosis in CHO-K1 cells.
Glycoprotein D and RSD Motif
- An important revelation of the research is about the EHV-1 envelope glycoprotein D (gD). It contains an RSD motif, which is a necessary component for the virus to enter cells via endocytosis.
- Mutational analysis was conducted to establish the critical role of this RSD motif in the process of endocytosis.
Endocytic Pathway and Viral Entry
- EHV-1 was shown to enter peripheral blood mononuclear cells primarily via the endocytic pathway, but it uses a different process for equine endothelial cells. For these, entry mainly occurs via fusion at the plasma membrane.
- The interaction between cellular integrins and the RSD motif present in gD triggers the process of EHV-1 entry via endocytosis.
Implication of the Study
- The data in this study reinforce that EHV-1 uses different cellular entry pathways to infect varying target cell populations of its natural host. This understanding could lead to more effective viral treatment methods by inhibiting these entry pathways.
Cite This Article
APA
Van de Walle GR, Peters ST, VanderVen BC, O'Callaghan DJ, Osterrieder N.
(2008).
Equine herpesvirus 1 entry via endocytosis is facilitated by alphaV integrins and an RSD motif in glycoprotein D.
J Virol, 82(23), 11859-11868.
https://doi.org/10.1128/JVI.00868-08 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
MeSH Terms
- Amino Acid Motifs
- Animals
- CHO Cells
- Cricetinae
- Cricetulus
- Endocytosis
- Flow Cytometry
- Herpesvirus 1, Equid / physiology
- Horses
- Integrin alphaV / physiology
- Oligopeptides / physiology
- Potassium / pharmacology
- Viral Envelope Proteins / chemistry
- Viral Envelope Proteins / physiology
Grant Funding
- P20 RR018724 / NCRR NIH HHS
- R01 AI022001 / NIAID NIH HHS
- AI-22001 / NIAID NIH HHS
- P20-RR-018724 / NCRR NIH HHS
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