Potential of DNA-mediated vaccination for equine herpesvirus 1

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

doi:10.1016/s0378-1135(99)00059-0

Cited by 16 publications

(5 citation statements)

References 42 publications

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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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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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“…More recently, the potential of DNA-mediated immunisation, baculovirus-expressed proteins or a combination was demonstrated in a murine model of respiratory infection and abortion (114,127,128,129,180). Inoculation of gD DNA also stimulated gD specific and VN responses in horses (128).…”

Section: Protection Against Abortionmentioning

confidence: 99%

Equine herpesvirus 1 and 4 infections: An update

Maanen

2002

Veterinary Quarterly

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Summary Equine herpesvirus 1 (EHV1) and equine herpesvirus 4 (EHV4) are important ubiquitous equine pathogens, causing much damage to the viral horse industry. EHV1 strains are associated with respiratory disease, abortion, and paresis/paralysis, whereas EHV4 strains are predominantly associated with respiratory disease. In the past decades much research effort has been put into improving knowledge about these viruses. In this paper the current state of knowledge of these viruses and the most important aspects of these virus infections, e.g. epidemiology, clinical aspects, pathogenesis and pathology, immunity, diagnosis, preventive management and management in the course of an outbreak and vaccination, is reviewed. Because we performed some research ourselves in the areas of diagnosis, epidemiology and vaccinology these aspects are reviewed in more depth than the other aspects. Still many questions have remained and new questions have risen. Consequently, research priorities should be made in an attempt to answer these questions. Therefore, this review ends with some personal recommendations for important priorities for future research.

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“…This supports the idea that HIV employs this endocytosis motif to evade the immune system and, importantly, this shows that mutation of these motifs may be a useful strategy to improve immunogenicity of vaccines. Therefore, our current finding that PRV gD encodes a functional endocytosis motif that, together with an endocytosis motif in gB, may reduce antibody-mediated elimination of the virus, may also be of significant importance for the construction of DNA vaccines encoding either gB or gD, which are generally considered to be potentially important vaccination strategies for many alphaherpesviruses, including PRV, bovine herpesvirus 1, equine herpesvirus 1, Marek's disease virus, and HSV (8,15,17,18,30,35,44,49).…”

Section: Vol 79 2005mentioning

confidence: 99%

Pseudorabies Virus Glycoprotein gD Contains a Functional Endocytosis Motif That Acts in Concert with an Endocytosis Motif in gB To Drive Internalization of Antibody-Antigen Complexes from the Surface of Infected Monocytes

Ficinska

Minnebruggen²,

Nauwynck³

et al. 2005

J Virol

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Viral glycoproteins gB and gD of the swine alphaherpesvirus pseudorabies virus (PRV), which is closely related to human herpes simplex virus and varicella-zoster virus, are able to drive internalization of antibodyantigen complexes that may form at the cell surface of infected monocytes, thereby protecting these cells from efficient antibody-mediated lysis. We found earlier that gB relies on an endocytosis motif in its cytoplasmic domain for its function during this internalization process. Here, we report that the PRV gD protein also contains a functional endocytosis motif (YRLL) in its cytoplasmic domain that drives spontaneous endocytosis of gD from the cell surface early in infection and that acts in concert with the endocytosis motif in gB to contribute to efficient internalization of antibody-antigen complexes in PRV-infected monocytes.Alphaherpesviruses have developed numerous strategies to delay or avoid recognition and elimination by different components of the immune system (11,21,45). The swine alphaherpesvirus pseudorabies virus (PRV) especially excels at circumventing antibody-dependent immunity, which allows it to replicate and sometimes spread in pigs that have been vaccinated with an inactivated vaccine (26, 48). PRV-infected blood monocytes play a pivotal role in spread of PRV in the presence of virus-neutralizing antibodies and carry the virus via the blood throughout the body (26).In PRV-infected blood monocytes, like in other PRV-infected cells, newly produced viral envelope proteins are incorporated in the plasma membrane (12,24), thereby rendering the cell recognizable for antibody-dependent immunity (13).However, we found earlier that binding of virus-specific antibodies to viral cell surface proteins in PRV-infected blood monocytes leads to rapid internalization of the antibody-antigen complexes (12), thereby lowering the susceptibility of the infected cell towards antibody-mediated cell lysis (41). This internalization process was found to be clathrin mediated and to depend on two of the PRV proteins at the cell surface, gB and gD (42).Clathrin-mediated endocytosis of cellular transmembrane proteins typically depends on so-called endocytosis motifs in their cytoplasmic domain, most notably YXXL and LL motifs (Y standing for tyrosine, L for leucine, and X for any amino acid). These motifs initiate endocytosis by establishing an interaction with the clathrin-associated AP-2 adaptor complex as a first step in the formation of clathrin-coated vesicles (3,4,20,36).We found that the function of gB in internalization of antibody-antigen complexes from the surface of PRV-infected monocytes depends on a functional tyrosine-based endocytosis motif (YQRL) in its cytoplasmic domain (10), and this motif was found to allow an interaction between gB and the AP-2 complex (43).How PRV gD is involved in internalization of antibodyantigen complexes, on the other hand, is unknown. PRV gD is a type I membrane glycoprotein of 402 amino acids, consisting of an extracellular domain, transmembrane region, and a ...

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Potential of DNA-mediated vaccination for equine herpesvirus 1

Cited by 16 publications

References 42 publications

Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

Equine herpesvirus 1 and 4 infections: An update

Pseudorabies Virus Glycoprotein gD Contains a Functional Endocytosis Motif That Acts in Concert with an Endocytosis Motif in gB To Drive Internalization of Antibody-Antigen Complexes from the Surface of Infected Monocytes

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