Pathogenicity and immunogenicity of equine herpesvirus type 1 mutants defective in either gI or gE gene in murine and hamster models.
Abstract: To develop a live vaccine for equine herpesvirus type 1 (EHV-1), two EHV-1 mutants containing no heterogeneous DNA, DeltagI and DeltagE, were constructed with deletions in the open reading frame of either glycoprotein I (gI) or E (gE), respectively. In equine cell culture, deletion mutants formed smaller plaques than the parental and revertant viruses, but the one-step growth patterns of the deletion mutants and the parental strain were approximately the same. These results suggest that both gI and gE contribute to the ability of EHV-1 to spread directly from cell-to-cell, but that these glycoproteins are not required for viral growth in vitro. Mice and hamsters inoculated intranasally with these mutants showed no clinical signs, and continued to gain weight, whereas those inoculated with the parental virus exhibited a reduction in mean body weight. Furthermore, nervous manifestations were observed in hamsters inoculated with the parental virus. These results suggest that gI and gE have an important role in EHV-1 virulence including neurovirulence in experimental animal models. On the other hand, serum neutralizing antibodies were detected in mice immunized with DeltagI or DeltagE at two weeks after inoculation. Following challenge with the parental virus, DeltagI- or DeltagE-immunized mice were able to clear parental virus from their lungs faster than mock-immunized mice. These results suggest that the EHV-1 mutants defective in gI and in gE are attenuated but have ability to elicit immune responses in inoculated mice that contribute to virus clearance.
Publication Date: 2006-11-07 PubMed ID: 17085880DOI: 10.1292/jvms.68.1029Google Scholar: Lookup
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- Journal Article
Summary
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The study presents the development and testing of two equine herpesvirus type 1 (EHV-1) mutants used to create a live vaccine for the virus. Though these mutants showed reduced cell-to-cell spread, they were just as capable of growth in-vitro as the parental EHV-1 strain and were less virulent in animal models. However, they still produced an immune response that helped clear out the parental virus.
Construction and observation of EHV-1 mutants
- The researchers created two EHV-1 mutants, called DeltagI and DeltagE. Each had deletions in either the glycoprotein I (gI) or E (gE) gene respectively.
- In comparison to the parental and revertant strains, these mutants created smaller plaques in equine cell culture.
- The growth patterns of the mutants and the parental strain were virtually the same when cultured. This indicates that while gI and gE contribute to the EHV-1’s ability to spread from cell to cell, they are not necessary for in-vitro viral growth.
Testing of EHV-1 mutants in animals
- Mice and hamsters that were intranasally inoculated with the DeltagI and DeltagE mutants did not show any clinical symptoms and continued to gain weight.
- Comparatively, animals inoculated with the parental virus displayed a decrease in average body weight. Nervous symptoms were also observed in hamsters infected with the parental EHV-1.
- This suggests that gI and gE play a significant role in EHV-1’s virulence and neurovirulence in experimental animal models.
Immune response to EHV-1 mutants
- Serum neutralizing antibodies against EHV-1 were found in mice that had been immunized with either DeltagI or DeltagE, two weeks post-inoculation.
- When challenged with the parental virus, these immunized mice were able to clear the virus from their lungs quicker than mice that had not been immunized (mock-immunized mice).
- This indicates that the EHV-1 mutants are attenuated but still able to elicit an immune response in the inoculated animals, aiding in virus clearance.
Cite This Article
APA
Tsujimura K, Yamanaka T, Kondo T, Fukushi H, Matsumura T.
(2006).
Pathogenicity and immunogenicity of equine herpesvirus type 1 mutants defective in either gI or gE gene in murine and hamster models.
J Vet Med Sci, 68(10), 1029-1038.
https://doi.org/10.1292/jvms.68.1029 Publication
Researcher Affiliations
- Molecular Biology Division, Epizootic Research Center, Equine Research Institute, Japan Racing Association, Tochigi, Japan.
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Cricetinae
- DNA, Viral / chemistry
- DNA, Viral / genetics
- Female
- Herpesviridae Infections / immunology
- Herpesviridae Infections / prevention & control
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / virology
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / immunology
- Herpesvirus Vaccines / immunology
- Horse Diseases / immunology
- Horse Diseases / virology
- Horses
- Immunization
- Male
- Mesocricetus
- Mice
- Mice, Inbred BALB C
- Mutagenesis, Insertional
- Neutralization Tests
- Specific Pathogen-Free Organisms
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / immunology
- Virulence
Citations
This article has been cited 3 times.- Awasthi S, Friedman HM. Molecular association of herpes simplex virus type 1 glycoprotein E with membrane protein Us9.. Arch Virol 2016 Nov;161(11):3203-13.
- McGraw HM, Awasthi S, Wojcechowskyj JA, Friedman HM. Anterograde spread of herpes simplex virus type 1 requires glycoprotein E and glycoprotein I but not Us9.. J Virol 2009 Sep;83(17):8315-26.
- Fulton A, Peters ST, Perkins GA, Jarosinski KW, Damiani A, Brosnahan M, Buckles EL, Osterrieder N, Van de Walle GR. Effective treatment of respiratory alphaherpesvirus infection using RNA interference.. PLoS One 2009;4(1):e4118.
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