DNA-mediated immunization with glycoprotein D of equine herpesvirus 1 (EHV-1) in a murine model of EHV-1 respiratory infection

Ruitenberg, K. M.; Walker, Clinton; Wellington, J. E.; Love, Daria N.; Whalley, J. M.

doi:10.1016/s0264-410x(98)00192-3

Cited by 39 publications

(15 citation statements)

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“…Such approach has already been reported for canine influenza, equine influenza virus, West Nile virus and bovine viral diarrhea virus, where virulence genes of these viruses were inserted into an equine herpesvirus type 1 (EHV1) vaccine [142-145]. The rationale behind the insertion of MYXV immunogenic genes into an equine pathogen is based on the fact that EHV1 grows extremely well in rabbit cells and hence, rabbit kidney (RK13) are the most commonly used in vitro cell line to grow EHV1 [146,147]. Still, despite this efficient growth in vitro, it needs to be determined whether EHV1 is capable of inducing robust immune responses in rabbits in vivo.…”

Section: Discussionmentioning

confidence: 99%

The current status and future directions of myxoma virus, a master in immune evasion

Spiesschaert

McFadden

Hermans

et al. 2011

Vet Res

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Myxoma virus (MYXV) gained importance throughout the twentieth century because of the use of the highly virulent Standard Laboratory Strain (SLS) by the Australian government in the attempt to control the feral Australian population of Oryctolagus cuniculus (European rabbit) and the subsequent illegal release of MYXV in Europe. In the European rabbit, MYXV causes a disease with an exceedingly high mortality rate, named myxomatosis, which is passively transmitted by biting arthropod vectors. MYXV still has a great impact on European rabbit populations around the world. In contrast, only a single cutaneous lesion, restricted to the point of inoculation, is seen in its natural long-term host, the South-American Sylvilagus brasiliensis and the North-American S. Bachmani. Apart from being detrimental for European rabbits, however, MYXV has also become of interest in human medicine in the last two decades for two reasons. Firstly, due to the strong immune suppressing effects of certain MYXV proteins, several secreted virus-encoded immunomodulators (e.g. Serp-1) are being developed to treat systemic inflammatory syndromes such as cardiovascular disease in humans. Secondly, due to the inherent ability of MYXV to infect a broad spectrum of human cancer cells, the live virus is also being developed as an oncolytic virotherapeutic to treat human cancer. In this review, an update will be given on the current status of MYXV in rabbits as well as its potential in human medicine in the twenty-first century.Table of contentsAbstract1. The virus2. History3. Pathogenesis and disease symptoms4. Immunomodulatory proteins of MYXV4.1. MYXV proteins with anti-apoptotic functions4.1.1. Inhibition of pro-apoptotic molecules4.1.2. Inhibition by protein-protein interactions by ankyrin repeat viral proteins4.1.3. Inhibition of apoptosis by enhancing the degradation of cellular proteins4.1.4. Inhibition of apoptosis by blocking host Protein Kinase R (PKR)4.2. MYXV proteins interfering with leukocyte chemotaxis4.3. MYXV serpins that inhibit cellular pro-inflammatory or pro-apoptotic proteases4.4. MYXV proteins that interfere with leukocyte activation4.5. MYXV proteins with sequence similarity to HIV proteins4.6. MYXV proteins with unknown immune function5. Vaccination strategies against myxomatosis5.1. Current MYXV vaccines5.2. Vaccination campaigns to protect European rabbits in the wild6. Applications of myxoma virus for human medicine6.1. MYXV proteins as therapeutics for allograft vasculopathy and atherosclerosis6.2. Applications for MYXV as a live oncolytic virus to treat cancer7. Discussion and Conclusions8. List of AbbreviationsReferencesAuthor DetailsAuthors' contributionsCompeting interestsFigure LegendsAcknowledgements

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Section: Discussionmentioning

confidence: 99%

The current status and future directions of myxoma virus, a master in immune evasion

Spiesschaert

McFadden

Hermans

et al. 2011

Vet Res

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“…A murine model was used to assess whether siRNA treatment is also effective in vivo. This mouse model of EHV-1 infection, first described by Awan et al in 1990 [22], has been intensively used to predict the efficacy of putative EHV-1 vaccines in horses [23][24][25][26], as well as the virulence potential of several EHV-1 strains [27][28][29][30][31][32]. In the present study, mice were anaesthetized and inoculated intranasally with siRNA's, followed by infection with 1610 5 PFU Ab4 by the same route.…”

Section: Intranasal Administration Of Sirna Reduces Clinical Sings Anmentioning

confidence: 96%

Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

et al. 2009

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BackgroundEquine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model.Methodology/Principal FndingssiRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection.Conclusions/SignificancesiRNA treatment has potential for both prevention and early treatment of EHV-1 infections.

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“…VC2-EHV-1-gD stimulated strong virus-neutralizing (VN) activity in comparison to that seen in both unvaccinated and VC2-vaccinated animals, and this VN activity was similar to that generated by the commercial EHV-1 killed virus vaccine. It has been reported that intranasal or intramuscular immunization with EHV-1 gD produces antigen-specific IgG responses (3,4,8,10,11,(22)(23)(24)(25). In addition, the presence of VN antibody prior to EHV-1 infection was shown to be associated with a reduction in the amount and duration of nasopharyngeal virus shedding (26,27).…”

Section: Figmentioning

confidence: 99%

Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice

Liu

Stanfield

Chouljenko

et al. 2017

J Virol

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Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the liveattenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHV XP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2-and mock-vaccinated animals (P Ͻ 0.01 or P Ͻ 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations (P Ͻ 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge (P Ͻ 0.01 or P Ͻ 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferonand tumor necrosis factor-positive CD4 ϩ T cells and CD8 ϩ T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals.IMPORTANCE A novel virus-vectored VC2-EHV-1-gD vaccine was constructed using the live-attenuated HSV-1 VC2 vaccine strain. This vaccine stimulated strong humoral and cellular immune responses in mice, suggesting that it could protect horses against EHV-1 infection.KEYWORDS EHV-1, HSV-1, equine herpesvirus, live vector vaccines, glycoprotein D, immune response, mouse model

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DNA-mediated immunization with glycoprotein D of equine herpesvirus 1 (EHV-1) in a murine model of EHV-1 respiratory infection

Cited by 39 publications

References 34 publications

The current status and future directions of myxoma virus, a master in immune evasion

The current status and future directions of myxoma virus, a master in immune evasion

Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice

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