Pseudorabies Virus Triggers Glycoprotein gE-Mediated ERK1/2 Activation and ERK1/2-Dependent Migratory Behavior in T Cells
Open accessAbstract
The interaction between viruses and immune cells of the host may lead to modulation of intracellular signaling pathways and to subsequent changes in cellular behavior that are of benefit for either virus or host. ERK1/2 (extracellular signal regulated kinase 1/2) signaling represents one of the key cellular signaling axes. Here, using wild-type and gE null virus, recombinant gE, and gE-transfected cells, we show that the gE glycoprotein of the porcine Varicellovirus pseudorabies virus (PRV) triggers ERK1/2 phosphorylation in Jurkat T cells and primary porcine T lymphocytes. PRV-induced ERK1/2 signaling resulted in homotypic T cell aggregation and increased motility of T lymphocytes. Our study reveals a new function of the gE glycoprotein of PRV and suggests that PRV, through activation of ERK1/2 signaling, has a substantial impact on T cell behavior. IMPORTANCE Herpesviruses are known to be highly successful in evading the immune system of their hosts, subverting signaling pathways of the host to their own advantage. The ERK1/2 signaling pathway, being involved in many cellular processes, represents a particularly attractive target for viral manipulation. Glycoprotein E (gE) is an important virulence factor of alphaherpesviruses, involved in viral spread. In this study, we show that gE has the previously uncharacterized ability to trigger ERK1/2 phosphorylation in T lymphocytes. We also show that virus-induced ERK1/2 signaling leads to increased migratory behavior of T cells and that migratory T cells can spread the infection to susceptible cells. In conclusion, our results point to a novel function for gE and suggest that virus-induced ERK1/2 activation may trigger PRV-carrying T lymphocytes to migrate and infect other cells susceptible to PRV replication.
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Several herpesviruses, such as PRV, HSV-1, HHV-8, and HCMV, activate integrin-mediated ERK-MAPK and PI3K signaling pathways through interactions of viral glycoproteins with putative receptors on host cell plasma membranes.
“Several herpesviruses, such as pseudorabies virus (PRV), herpes simplex virus 1 (HSV-1), human herpesvirus 8 (HHV-8), and HCMV, have been reported to activate integrin-mediated ERK-MAPK and PI3K signaling pathways through the interactions of viral glycoproteins with putative receptors present at the plasma membranes of host cells (23, 28, 33-35).”
From Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a <sup>+</sup> Monocytic Cells upon Adhesion to Endothelial Cells (2015) · cites this paper as [23]
The Discussion (p. 6) reports that PRV glycoprotein gE triggers ERK1/2 activation in T cells. It describes binding to an unidentified cell-surface receptor as speculative, and does not establish integrin-mediated signaling or PI3K activation. The same discussion does not establish the claimed mechanism for HSV-1, HHV-8, or HCMV. (LLM, conf=0.87)
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Laval, K., Favoreel, H. W., Poelaert, K. C. K., Van Cleemput, J., & Nauwynck, H. J. (2015) · Journal of Virology · doi:10.1128/jvi.01589-15 · Cited by 43 · see citing works
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- Authors
- Setas Pontes, M., Devriendt, B., & Favoreel, H. W.
- Affiliations
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- Ghent University (BE)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2015-02-15
- Volume
- 89
- Issue
- 4
- Pages
- 2149-2156
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC4338889
- OpenAlex
- W2095869412
- Cited by
- 15
- References
- 58
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 1 · 2020: 2 · 2018: 4 · 2017: 2 · 2015: 2
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- pseudorabies virus, glycoprotein E, ERK signaling, T cell migration, alphaherpesvirus, viral spread, T cells
- MeSH terms
- Animals, Cell Movement, Cells, Cultured, Humans, Herpesvirus 1, Suid, Swine, T-Lymphocytes, Viral Envelope Proteins, Gene Deletion, MAP Kinase Signaling System, Host-Pathogen Interactions
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