Equine Herpesvirus 1 Entry via Endocytosis Is Facilitated by αV Integrins and an RSD Motif in Glycoprotein D
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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 αVβ5, 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.
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EHV-1 envelope glycoprotein D (gD) interacts with αV integrins present on PBMC and is critical for viral entry via endocytosis.
“To date, the EHV-1 envelope glycoprotein D (gD) has been shown to interact with 𝛂 V integrins present on PBMC and to be critical for viral entry via endocytosis (36).”
From Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a <sup>+</sup> Monocytic Cells upon Adhesion to Endothelial Cells (2015) · cites this paper as [36]
Interaction between αvβ3 integrin present on PBMC and the RSD motif present in EHV-1 gD triggers EHV-1 entry via endocytosis.
“The interaction between αvβ3 integrin present on PBMC and the arginine, serine and aspartic acid (RSD) motif present in EHV-1 gD is known to trigger EHV-1 entry via endocytosis (Van de Walle et al., 2008).”
From The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1 (2021) · cites this paper as Van de Walle et al., 2008
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References 50 · Cited by 54
- Authors
- Van de Walle, G. R., Peters, S. T., VanderVen, B. C., O'Callaghan, D. J., & Osterrieder, N.
- Affiliations
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853
- Cornell University (US)
- Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130
- Corresponding author
- Osterrieder, Nikolaus
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2008-12
- Volume
- 82
- Issue
- 23
- Pages
- 11859-11868
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC2583640
- OpenAlex
- W2167727704
- Cited by
- 54
- References
- 50
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- National Institutes of Health (5p20rr018724-07)
- National Institute of Allergy and Infectious Diseases (AI 22001, R01AI022001)
- National Center for Research Resources (P20-RR018724)
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- equine herpesvirus 1, alphaherpesvirus, viral entry, endocytosis, ITGAV, RGD motif, glycoprotein D, cell fusion, peripheral blood mononuclear cells, endothelial cells, CHO-K1 cells
- MeSH terms
- Animals, Cricetulus, Endocytosis, Herpesvirus 1, Equid, Flow Cytometry, Cricetinae, Horses, Oligopeptides, Potassium, Viral Envelope Proteins, CHO Cells, Amino Acid Motifs, Integrin alphaV
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