In vitro and in vivo characterization of equine herpesvirus type 1 (EHV-1) mutants devoid of the viral chemokine-binding glycoprotein G (gG).

von Einem, Jens; Smith, Patrick M.; Van de Walle, Gerlinde R.; O'Callaghan, Dennis J.; Osterrieder, Nikolaus

doi:10.1016/j.virol.2006.12.008

Cited by 37Herpesvirus Infections and TreatmentsAnimal Virus Infections StudiesViral-associated cancers and disorders

In vitro and in vivo characterization of equine herpesvirus type 1 (EHV-1) mutants devoid of the viral chemokine-binding glycoprotein G (gG).

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von Einem, Jens, Smith, Patrick M., Van de Walle, Gerlinde R., O'Callaghan, Dennis J., Osterrieder, Nikolaus·2007·Virology

DOI 10.1016/j.virol.2006.12.008

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Abstract

Glycoprotein G (gG) of equine herpesvirus type 1 (EHV-1), a structural component of virions and secreted from virus-infected cells, was shown to bind to a variety of different chemokines and as such might be involved in immune modulation. Little is known, however, about its role in the replication cycle and infection of EHV-1 in vivo. Here we report on the function of gG in context of virus infection in vitro and in vivo. A gG deletion mutant of pathogenic EHV-1 strain RacL11 (vL11DeltagG) was constructed and analyzed. Deletion of gG had virtually no effect on the growth properties of vL11DeltagG in cell culture when compared to parental virus or a rescuant virus vL11DeltagGR, respectively, and virus titers and plaque formation were unaffected in the absence of the glycoprotein. Similarly, in the murine model of EHV-1 infection, no significant differences in virulence between the gG deletion mutant and RacL11 or vL11DeltagGR were found at high doses of infection. However, infection of mice at lower doses revealed that the gG deletion mutant was able to replicate to higher titers in lungs of infected mice. Additionally, these mice lost significantly more weight than those infected with RacL11 and a more pronounced inflammatory response in lungs was observed. Therefore we concluded that deletion of gG in EHV-1 seems to lead to an exacerbation of respiratory disease in the mouse.

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In vivo, an EHV-1 gG deleted mutant induces a more pronounced inflammatory response compared to the wild-type virus.
“In vivo, an EHV-1 gG deleted mutant induces a more pronounced inflammatory response compared to the wild-type virus (von Einem et al., 2007).”
From The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1 (2021) · cites this paper as von Einem et al., 2007
In “Absence of gG exacerbates respiratory disease at lower doses of infection” (page not provided), the paper reports greater lung inflammation with the gG-deleted virus than with parental RacL11 at lower infection doses. It also reports no difference at a high dose, a qualification the citing sentence omits. (LLM, conf=0.90)
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Background
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“(PAGE) exactly as described before (83).”
Method
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
Spiesschaert, B., Osterrieder, N., & Azab, W. (2015) · Viruses · doi:10.3390/v7020522 · Cited by 24 · see citing works
“004% bromophenol blue) was added to lysates, the mixture was heated at 95 °C for 5 min, and proteins were separated by 10% SDS-polyacrylamide gel electrophoresis (PAGE) as described before [46].”
The role of glycoprotein H of equine herpesviruses 1 and 4 (EHV-1 and EHV-4) in cellular host range and integrin binding
Azab, W., Zajic, L. B., & Osterrieder, N. (2012) · Veterinary Research · doi:10.1186/1297-9716-43-61 · Cited by 19 · see citing works
“004% bromophenol blue) was added, the mixture was heated at 95 °C for 5 min and proteins were separated by 10% SDS-polyacrylamide gel electrophoresis (PAGE) exactly as previously described [35].”
Method
Analysis of the Herpesvirus Chemokine-binding Glycoprotein G Residues Essential for Chemokine Binding and Biological Activity
de Walle, G. R. V., Kaufer, B. B., Chbab, N., & Osterrieder, N. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m808127200 · Cited by 17 · see citing works
The role of secreted glycoprotein G of equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) in immune modulation and virulence
Thormann, N., de Walle, G. R. V., Azab, W., & Osterrieder, N. (2012) · Virus Research · doi:10.1016/j.virusres.2012.07.029 · Cited by 14 · see citing works
Equine herpesvirus 1 infection orchestrates the expression of chemokines in equine respiratory epithelial cells
Poelaert, K. C. K., Cleemput, J. V., Laval, K., Xie, J., Favoreel, H. W., & Nauwynck, H. (2019) · Journal of General Virology · doi:10.1099/jgv.0.001317 · Cited by 10 · see citing works
Equine herpesvirus type 1 (EHV-1) open reading frame 59 encodes an early protein that is localized to the cytosol and required for efficient virus growth
Said, A., & Osterrieder, N. (2013) · Virology · doi:10.1016/j.virol.2013.11.035 · Cited by 9 · see citing works
Ubiquitination and degradation of the ORF34 gene product of equine herpesvirus type 1 (EHV-1) at late times of infection
Said, A., DAMIANI, A. M., & Osterrieder, N. (2014) · Virology · doi:10.1016/j.virol.2014.05.009 · Cited by 8 · see citing works
Glycoprotein B of equine herpesvirus type 1 has two recognition sites for subtilisin-like proteases that are cleaved by furin
Spiesschaert, B., Stephanowitz, H., Krause, E., Osterrieder, N., & Azab, W. (2016) · Journal of General Virology · doi:10.1099/jgv.0.000418 · Cited by 5 · see citing works
“Sample buffer [1 M Tris/HCl (pH 6.8), 0.8 % SDS, 0.4 % glycerol, 0.15 % b-mercaptoethanol, 0.004 % bromophenol blue] was added, the mixture was heated at 95 uC for 5 min and proteins were separated by 10 % SDSPAGE as described before (von Einem et al., 2007).”
MethodInfluential
Chemokine-binding proteins encoded by herpesviruses
Benko, M., Lenhartová, S., Kempová, V., Betáková, T., & Kúdelová, M. (2020) · Acta Virologica · doi:10.4149/av_2020_213 · Cited by 4 · see citing works
Equine Herpesvirus Infections: Treatment Progress and Challenges in Horses and Donkeys
Khan, M. Z., Ji, Y., Fan, X., Liu, Y., Liu, W., & Wang, C. (2025) · Veterinary Sciences · doi:10.3390/vetsci12111082 · Cited by 5 · see citing works
“Deletion studies of gG demonstrate enhanced inflammatory responses and increased immune cell migration to infected sites [86,186].”
Equid herpesvirus type 3 infection produces membrane-associated and secreted forms of glycoprotein G that are not required for efficient cell-to-cell spread of the virus in vitro
Losinno, A. D., Vissani, M. A., Sanchez, D., & DAMIANI, A. M. (2023) · Archives of Virology · doi:10.1007/s00705-023-05727-4 · Cited by 2 · see citing works
Equine Herpesviruses
Gulati, B. R., Virmani, N., & Tripathi, B. N. (2019) · Springer eBooks · doi:10.1007/978-981-13-9073-9_4 · Cited by 1 · see citing works
Regulatory Strategies and Factors Affecting Veterinary Viral Vector Development
Bublot, M., Woerly, V., Wang, Q., & King, H. (2020) · Springer eBooks · doi:10.1007/978-3-030-51927-8_13 · Cited by 1 · see citing works
Chemokines and Viral Infections
Alcamı́, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-374279-7.14013-5 · Cited by 1 · see citing works
Development of a vectored equine herpesvirus type 1 (EHV-1) vaccine against pandemic influenza A virus (09/H1N1)
Said, A. (2013) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-10249
Profiling Chemokine–Glycoprotein G Interactions: Implications for Alphaherpesviral Immune Evasion
de Walle, G. R. V., & Osterrieder, N. (2012) · Future Virology · doi:10.2217/fvl.12.31
Functions of glycoprotein G of herpes simplex virus type 2
Görander, S. (2010) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Respuesta inmune local en la patogenia del aborto inducido por herpesvirus equino 1
Bravi, M. E. (2018) · doi:10.35537/10915/65953

The role of the secreted glycoprotein G (gG) in equine herpesvirus type 1 (EHV-1) immune modulation and virulence
Thormann, N. (2012) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-12919
The role of secreted glycoprotein G of equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) in immune modulation and virulence
Thormann, N., de Walle, G. R. V., Azab, W., & Osterrieder, N. (2012) · Virus Research · doi:10.1016/j.virusres.2012.07.029 · Cited by 14 · see citing works
Construction and characterization of an equine herpesvirus 1 glycoprotein C negative mutant
Osterrieder, N. (1999) · Virus Research · doi:10.1016/s0168-1702(98)00134-8 · Cited by 84 · see citing works
Pathogenicity and Immunogenicity of Equine Herpesvirus Type 1 Mutants Defective in Either gI or gE Gene in Murine and Hamster Models
Tsujimura, K., Yamanaka, T., Kondo, T., Fukushi, H., & Matsumura, T. (2006) · Journal of Veterinary Medical Science · doi:10.1292/jvms.68.1029 · Cited by 25 · see citing works
Contribution of gene products encoded within the unique short segment of equine herpesvirus 1 to virulence in a murine model
Frampton, A. R., Smith, P. M., Zhang, Y., Matsumura, T., Osterrieder, N., & O’Callaghan, D. J. (2002) · Virus Research · doi:10.1016/s0168-1702(02)00245-9 · Cited by 30 · see citing works

Authors: von Einem, J., Smith, P. M., Van de Walle, G. R., O'Callaghan, D. J., & Osterrieder, N.
Affiliations: Louisiana State University (US)
Cornell University (US)
Corresponding author: Osterrieder, Nikolaus
ORCID: Smith, Patrick M.
Osterrieder, Nikolaus
Venue: Virology
Publisher: Elsevier BV
Published: 2007-05
Volume: 362
Issue: 1
Pages: 151-162
ISSN: 0042-6822 (ISSN-L)
DOI: 10.1016/j.virol.2006.12.008
OpenAlex: W2063071600
Cited by: 37
References: 52
Citations by year: 2025: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 5
FWCI: 2.52
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2305 d)
Locations: Virology (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 › Oncology › Viral-associated cancers and disorders
Keywords: equine herpesvirus 1, glycoprotein G, chemokine binding, viral virulence, respiratory diseases, immunomodulation, mouse infection model, inflammation
MeSH terms: Animals, Body Weight, Cell Line, Disease Models, Animal, Herpesvirus 1, Equid, Female, Herpesviridae Infections, Histocytochemistry, Lung, Mice, Inbred BALB C, Microscopy, Viral Plaque Assay, Rabbits, Viral Envelope Proteins, Virulence, Gene Deletion, Mice

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In vitro and in vivo characterization of equine herpesvirus type 1 (EHV-1) mutants devoid of the viral chemokine-binding glycoprotein G (gG).

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