Genetic immunisation of cattle against bovine herpesvirus 1: glycoprotein gD confers higher protection than glycoprotein gC or tegument protein VP8.

in Veterinary Research (2005), 36(4), 529-44

Bovine herpesvirus 1 (BoHV-1) has frequently been used as a model for testing parameters affecting DNA immunisation in large animals like cattle. However, the selection of target antigens has been poorly ... [more ▼]

Bovine herpesvirus 1 (BoHV-1) has frequently been used as a model for testing parameters affecting DNA immunisation in large animals like cattle. However, the selection of target antigens has been poorly studied, and most of the experiments have been conducted in mice. In the present study, we demonstrated in cattle that a DNA vaccine encoding BoHV-1 glycoprotein gD induces higher neutralising antibody titres than vaccines encoding BoHV-1 gC. Additionally, we show that a DNA vaccine encoding a secreted form of gD induces a higher immune response than a vaccine encoding full-length gD. However, the enhanced immunogenicity associated with the secretion of gD could not be extended to the glycoprotein gC. The current study also describes for the first time the development and the evaluation of a DNA vaccine encoding the major tegument protein VP8. This construct, which is the first BoHV-1 plasmid vaccine candidate that is not directed against a surface glycoprotein, induced a high BoHV-1 specific cellular immunity but no humoral immune response. The calves vaccinated with the constructs encoding full-length and truncated gD showed a non-significant tenfold reduction of virus excretion after challenge. Those calves also excreted virus for significantly (p < 0.05) shorter periods (1.5 days) than the non-vaccinated controls. The other constructs encoding gC and VP8 antigens induced no virological protection as compared to controls. Altogether the DNA vaccines induced weaker immunity and protection than conventional marker vaccines tested previously, confirming the difficulty to develop efficient DNA vaccines in large species. [less ▲]

STAT5 promotes granulocyte survival during inflammation

in Pflügers Archiv : European Journal of Physiology (2004), 447

The core 2 beta-1,6-N-acetylglucosaminyltransferase-M encoded by bovine herpesvirus 4 is not essential for virus replication despite contributing to post-translational modifications of structural proteins.

in Journal of General Virology (The) (2004), 85(Pt 2), 355-67

The Bo17 gene of bovine herpesvirus 4 (BoHV-4) is the only virus gene known to date that encodes a homologue of the cellular core 2 beta-1,6-N-acetylglucosaminyltransferase-mucine type (C2GnT-M). Recently ... [more ▼]

The Bo17 gene of bovine herpesvirus 4 (BoHV-4) is the only virus gene known to date that encodes a homologue of the cellular core 2 beta-1,6-N-acetylglucosaminyltransferase-mucine type (C2GnT-M). Recently, our phylogenetic study revealed that the Bo17 gene has been acquired from an ancestor of the African buffalo around 1.5 million years ago. Despite this recent origin, the Bo17 sequence has spread to fixation in the virus population possibly by natural selection. Supporting the latter hypothesis, it has been shown by our group for the V. test strain that Bo17 is expressed during BoHV-4 replication in vitro, and that Bo17 expression product (pBo17) has all three enzymic activities exhibited by cellular C2GnT-M, i.e. core 2, core 4 and I branching activities. In the present study, firstly it was investigated whether encoding a functional C2GnT-M is a general property of BoHV-4 strains. Analysis of nine representative strains of the BoHV-4 species revealed that all of them express the Bo17 gene and the associated core 2 branching activity during virus replication in vitro. Secondly, in order to investigate the roles of Bo17, its kinetic class of expression was analysed and a deleted recombinant strain was produced. These experiments revealed that Bo17 is expressed as an early gene which is not essential for virus replication in vitro. However, comparison of the structural proteins, produced by the wild-type, the revertant and the deleted viruses, by 2D gels demonstrated that pBo17 contributes to the post-translational modifications of structural proteins. Possible roles of Bo17 in vivo are discussed. [less ▲]

Investigation of the susceptibility of human cell lines to bovine herpesvirus 4 infection: Demonstration that human cells can support a nonpermissive persistent infection which protects them against tumor necrosis factor alpha-induced apoptosis

in Journal of Virology (2004), 78(5), 2336-2347

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that has a worldwide distribution in the population of cattle. Many factors make human contamination by BoHV-4 likely to occur. In this study, we ... [more ▼]

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that has a worldwide distribution in the population of cattle. Many factors make human contamination by BoHV-4 likely to occur. In this study, we performed in vitro experiments to assess the risk and the consequences of human infection by BoHV-4. First, by using a recombinant BoHV-4 strain expressing enhanced green fluorescent protein under the control of the human cytomegalovirus immediate-early gene promoter, we tested 21 human cell lines for their sensitivity and their permissiveness to BoHV-4 infection. These experiments revealed that human cell lines from lymphoid and myeloid origins were resistant to infection, whereas epithelial cells, carcinoma cells, or adenocarcinoma cells isolated from various organs were sensitive but poorly permissive to BoHV-4 infection. Second, by using the HeLa cell line as a model of human cells sensitive but not permissive to BoHV-4 infection, we investigated the resistance of infected cells to apoptosis and the persistence of the infection through cellular divisions. The results obtained can be summarized as follows. (i) BoHV-4 nonpermissive infection of HeLa cells protects them against tumor necrosis factor alpha-induced apoptosis. (ii) BoHV-4 infection of HeLa cells persists in cell culture; however, the percentage of infected cells decreases with time due to erratic transmission of the viral genome through cell division. (iii) BoHV-4 infection has no effect on the rate of HeLa cell division. Altogether, these data suggest that BoHV-4 could infect humans. This study also stresses the importance of considering the insidious effects of nonpermissive infection when the biosafety of animal gammaherpesviruses for humans is being considered. [less ▲]

Antiapoptotic effect of GM-CSF activated STAT5 signaling pathway in chronic mastitis-affected cows : possible involvement in persistent accumulation of neutrophils in milk

in Congress COST Action 844: “Apoptosis and programmed cell death : molecular mechanisms and applications in Biotechnology and Agriculture” (2004)

L’herpèsvirus bovin 4

in Annales de Médecine Vétérinaire (2003), 147(4), 215-247

Bovine herpesvirus 4 (BoHV-4) belongs to the Herpesviridae family, Gammaherpesvirinae subfamily, Rhadinovirus genus like human herpesvirus 8 (HHV-8), the causative agent of Kaposi's sarcoma. BoHV-4 has a ... [more ▼]

Bovine herpesvirus 4 (BoHV-4) belongs to the Herpesviridae family, Gammaherpesvirinae subfamily, Rhadinovirus genus like human herpesvirus 8 (HHV-8), the causative agent of Kaposi's sarcoma. BoHV-4 has a worldwide distribution in the cattle population. It has been isolated from cattle showing various clinical signs as well as from healthy cattle. The interest of the scientific community for BoHV-4 is explained by two reasons. Firstly, BoHV-4 represents an homologous virus/host species model to study the biology of gammaherpesviruses. Secondly, the use of BoHV-4 as a recombinant vector for expression both in vitro and in vivo has been proposed. For these reasons, a considerable amount of data has been collected on this virus. In the present paper, the authors will present a general overview of the literature published on this virus addressing clinical, epidemiological and fundamental aspects of BoHV-4. Finally, in the light of their recent phylogenetic data, the authors will discuss the origin and the host species of BoHV-4 leading to the conclusion that this virus should be considered as a virus of the African buffalo rather than cattle. [less ▲]