Herpesvirus chemokine-binding glycoprotein G (gG) efficiently inhibits neutrophil chemotaxis in vitro and in vivo.
Abstract: Glycoprotein G (gG) of alphaherpesviruses has been described to function as a viral chemokine-binding protein (vCKBP). More recently, mutant viruses devoid of gG have been shown to result in increased virulence, but it remained unclear whether the potential of gG to serve as a vCKBP is responsible for this observation. In this study, we used equine herpesvirus type 1 (EHV-1) as a model to study the pathophysiological importance of vCKBP activity. First, in vitro chemotaxis assays studying migration of immune cells, an important function of chemokines, were established. In such assays, supernatants of EHV-1-infected cells significantly inhibited IL-8-induced chemotaxis of equine neutrophils. Identification of gG as the responsible vCKBP was achieved by repeating similar experiments with supernatants from cells infected with a gG-negative mutant, which were unable to alter IL-8-induced equine neutrophil migration. Furthermore, rEHV-1 gG was able to significantly reduce neutrophil migration, establishing gG as a bona fide vCKBP. Second, and importantly, in vivo analyses in a murine model of EHV-1 infection showed that neutrophil migration in the target organ lung was significantly reduced in the presence of gG. In summary, we demonstrate for the first time that EHV-1 gG not only binds to chemokines but is also capable of inhibiting their chemotactic function both in vitro and in vivo, thereby contributing to viral pathogenesis and virulence.
Publication Date: 2007-09-06 PubMed ID: 17785855DOI: 10.4049/jimmunol.179.6.4161Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper investigates how the glycoprotein G (gG) of alphaherpesviruses inhibits the movement of immune cells, contributing to increased virulence of infections. The study uses the equine herpesvirus type 1 (EHV-1) as a model and demonstrates that its gG successfully interferes with both in vitro and in vivo activities of immune cells in response to viral infections.
Objective and Methodology
- The main objective of this study was to determine the role of viral chemokine-binding protein (vCKBP) gG, found in alphaherpesviruses, in inhibiting the chemotactic function of immune cells.
- This was accomplished by studying the activities of the equine herpesvirus type 1 (EHV-1) using both in vitro and in vivo models.
- The researchers performed chemotaxis assays, which measure the migration of cells in response to certain stimuli, in this case caused by infection with EHV-1.
In Vitro Findings
- In the in vitro tests, the researchers found that supernatants from EHV-1-infected cells considerably hindered the IL-8-induced chemotaxis of equine neutrophils, an important immune response to infection.
- This inhibitory effect was linked to gG, since when similar experiments were conducted with supernatants from cells infected with a gG-deficient mutant, they failed to alter the IL-8-induced movement of neutrophils.
- The researchers also discovered that recombinant EHV-1 gG could effectively limit neutrophil migration, confirming gG’s function as an integral vCKBP.
In Vivo Findings
- In vivo analysis in a mouse model of EHV-1 infection revealed that gG presence significantly reduced the migration of neutrophils in the target organ lung, confirming the in vitro findings.
- This significant reduction in neutrophil movement would limit the immune response to the viral infection, thus increasing the virulence of the disease.
Conclusion
- The study concludes that EHV-1 gG not only binds to chemokines but also hampers their chemotactic function both in vitro and in vivo, contributing to increased severity of viral infections.
- This study highlights the importance of studying the role of proteins like gG in virus pathogenesis, which can lead to better understanding and treatment of viral infections.
Cite This Article
APA
Van de Walle GR, May ML, Sukhumavasi W, von Einem J, Osterrieder N.
(2007).
Herpesvirus chemokine-binding glycoprotein G (gG) efficiently inhibits neutrophil chemotaxis in vitro and in vivo.
J Immunol, 179(6), 4161-4169.
https://doi.org/10.4049/jimmunol.179.6.4161 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
MeSH Terms
- Animals
- Binding, Competitive / immunology
- Cell Line
- Cell Migration Inhibition
- Cell-Free System / immunology
- Chemokine CCL2 / metabolism
- Chemokine CCL2 / physiology
- Chemokines / metabolism
- Chemotaxis, Leukocyte / immunology
- Female
- Herpesviridae Infections / immunology
- Herpesviridae Infections / metabolism
- Herpesviridae Infections / pathology
- Herpesvirus 1, Equid / immunology
- Herpesvirus 1, Equid / pathogenicity
- Horses
- Interleukin-8 / antagonists & inhibitors
- Interleukin-8 / physiology
- Mice
- Neutrophils / cytology
- Neutrophils / immunology
- Neutrophils / virology
- Pneumonia, Viral / immunology
- Pneumonia, Viral / metabolism
- Pneumonia, Viral / pathology
- Protein Binding / immunology
- Rabbits
- Viral Envelope Proteins / deficiency
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / metabolism
- Viral Envelope Proteins / physiology
- Virulence
Citations
This article has been cited 21 times.- Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G. A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.. Front Vet Sci 2021;8:674850.
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