Recombination in alphaherpesviruses

in Reviews in Medical Virology (2005), 15(2, Mar-Apr), 89-103

Within the Herpesviridae family, Alphaherpesvirinae is an extensive subfamily which contains numerous mammalian and avian viruses. Given the low rate of herpesvirus nucleotide substitution, recombination ... [more ▼]

Within the Herpesviridae family, Alphaherpesvirinae is an extensive subfamily which contains numerous mammalian and avian viruses. Given the low rate of herpesvirus nucleotide substitution, recombination can be seen as an essential evolutionary driving force although it is likely underestimated. Recombination in alphaherpesviruses is intimately linked to DNA replication. Both viral and cellular proteins participate in this recombination-dependent replication. The presence of inverted repeats in the alphaherpesvirus genomes allows segment inversion as a consequence of specific recombination between repeated sequences during DNA replication. High molecular weight intermediates of replication, called concatemers, are the site of early recombination events. The analysis of concatemers, from cells coinfected by two distinguishable alphaherpesviruses provides an efficient tool to study recombination without the bias introduced by invisible or non-viable recombinants, and by dominance of a virus over recombinants. Intraspecific recombination frequently occurs between strains of the same alphaherpesvirus species. Interspecific recombination depends on enough sequence similarity to enable recombination between distinct alphaherpesvirus species. The most important prerequisite for successful recombination is coinfection of the individual host by different virus strains or species. Consequently the following factors affecting the distribution of different viruses to shared target cells need to be considered: dose of inoculated virus, time interval between inoculation of the first and the second virus, distance between the marker mutations, genetic homology, virulence and latency. Recombination, by exchanging genomic segments, may modify the virulence of alphaherpesviruses. It must be carefully assessed for the biosafety of antiviral therapy, alphaherpesvirus-based vectors and live attenuated vaccines. Copyright (C) 2004 John Wiley Sons, Ltd. [less ▲]

Both soluble and membrane-anchored forms of Felid herpesvirus 1 glycoprotein G function as a broad-spectrum chemokine-binding protein

in Journal of General Virology (2005), 86(Pt 12), 3209-3214

Recently, glycoprotein G (gG) of several alphaherpesviruses infecting large herbivores was shown to belong to a new family of chemokine-binding proteins (vCKBPs). In the present study, the function of ... [more ▼]

Recently, glycoprotein G (gG) of several alphaherpesviruses infecting large herbivores was shown to belong to a new family of chemokine-binding proteins (vCKBPs). In the present study, the function of Felid herpesvirus 1 (FeHV-1) gG as a vCKBP was investigated and the following conclusions were reached: (i) FeHV-1 secreted gG is a high-affinity broad-spectrum vCKBP that binds CC, CXC and C chemokines; (ii) gG is the only vCKBP expressed by FeHV-1 that binds CCL3 and CXCL1; (iii) secreted gG blocks chemokine activity by preventing their interaction with high-affinity cellular receptors; (iv) the membrane-anchored form of gG expressed on the surface of infected cells is also able to bind chemokines; and (v) the vCKBP activity is conserved among different field isolates of FeHV-1. Altogether, these data demonstrate that FeHV-1 gG is a new member of the vCKBP-4 family. Moreover, this study is the first to demonstrate that gG expressed at the surface of FeHV-1-infected cells can also bind chemokines. [less ▲]

Les glycosyltransférases virales

in Virologie (2005), 9(1), 35-48

Les glycanes constituent une classe biochimique difficile à investiguer, mais dont les rôles essentiels à tous les niveaux de la biologie se sont imposés comme une évidence ces dernières décennies. Il ... [more ▼]

Les glycanes constituent une classe biochimique difficile à investiguer, mais dont les rôles essentiels à tous les niveaux de la biologie se sont imposés comme une évidence ces dernières décennies. Il apparaît maintenant qu'ils représentent la quatrième catégorie de molécules bio-informatives après l'ADN, l'ARN et les protéines. À ce titre, après la génomique, la transcriptomique et la protéomique, l'ère de la glycomique est appelée à concentrer beaucoup d'intérêts. Des millions d'années durant, les virus ont co-évolué avec leurs hôtes; au cours de ce processus adaptatif, ils ont évolué de manière à favoriser leur multiplication par l'acquisition de moyens visant à imiter, détourner ou saboter les mécanismes les plus complexes de la physiologie de leurs hôtes, y compris les mécanismes destinés à interférer avec le glycome. La découverte de l'importance du glycome dans le contexte de la régulation des interactions entre les virus et leurs hôtes a récemment mené à la notion de « glycovirologie ». Un aspect fascinant de la glycovirologie est l'étude des mécanismes viraux visant à modifier le glycome. Les virus affectent le glycome de deux façons: en régulant l'expression des glycosyltransférases de la cellule hôte ou en exprimant leur propre glycosyltransférase. Cette revue est consacrée aux glycosyltransférases virales et à la description de leurs fonctions. La description de ces enzymes illustre différents concepts fondamentaux de virologie et démontre indirectement le rôle crucial joué par la glycomique dans les processus biologiques. [less ▲]

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 ▲]

Superinfection prevents recombination of the alphaherpesvirus bovine herpesvirus 1

in Journal of Virology (2004), 78(8), 3872-3879

Homologous recombination between strains of the same alphaherpesvirus species occurs frequently both in vitro and in vivo. This process has been described between strains of herpes simplex virus type 1 ... [more ▼]

Homologous recombination between strains of the same alphaherpesvirus species occurs frequently both in vitro and in vivo. This process has been described between strains of herpes simplex virus type 1, herpes simplex virus type 2, pseudorabies virus, feline herpesvirus 1, varicella-zoster virus, and bovine herpesvirus 1 (BoHV-1). In vivo, the rise of recombinant viruses can be modulated by different factors, such as the dose of the inoculated viruses, the distance between inoculation sites, the time interval between inoculation of the first and the second virus, and the genes in which the mutations are located. The effect of the time interval between infections with two distinguishable BoHV-1 on recombination was studied in three ways: (i) recombination at the level of progeny viruses, (ii) interference induced by the first virus infection on beta-gallactosidase gene expression of a superinfecting virus, and (iii) recombination at the level of concatemeric DNA. A time interval of 2 to 8 h between two successive infections allows the establishment of a barrier, which reduces or prevents any successful superinfection needed to generate recombinant viruses. The dramatic effect of the time interval on the rise of recombinant viruses is particularly important for the risk assessment of recombination between glycoprotein E-negative marker vaccine and field strains that could threaten BoHV-1 control and eradication programs. [less ▲]

Ceramides play a critical role in spontaneous neutrophil apoptosis

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

STAT5 promotes granulocyte survival during inflammation

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

Glycosyltransferases encoded by viruses.

in Journal of General Virology (The) (2004), 85(Pt 10), 2741-54

Studies of cellular biology in recent decades have highlighted the crucial roles of glycans in numerous important biological processes, raising the concept of glycomics that is now considered as important ... [more ▼]

Studies of cellular biology in recent decades have highlighted the crucial roles of glycans in numerous important biological processes, raising the concept of glycomics that is now considered as important as genomics, transcriptomics and proteomics. For millions of years, viruses have been co-evolving with their hosts. Consequently, during this co-evolution process, viruses have acquired mechanisms to mimic, hijack or sabotage host processes that favour their replication, including mechanisms to modify the glycome. The importance of the glycome in the regulation of host-virus interactions has recently led to a new concept called 'glycovirology'. One fascinating aspect of glycovirology is the study of how viruses affect the glycome. Viruses reach that goal either by regulating expression of host glycosyltransferases or by expressing their own glycosyltransferases. This review describes all virally encoded glycosyltransferases and discusses their established or putative functions. The description of these enzymes illustrates several intriguing aspects of virology and provides further support for the importance of glycomics in biological processes. [less ▲]

Bovine herpesvirus 1 glycoprotein D expression in bovine upper respiratory tract mediated by a human adenovirus type 5

in Veterinary Research (2004), 35(6, Nov-Dec), 715-721

Bovine herpesvirus 1 glycoprotein D (gD) gene expression by recombinant replication defective human adenovirus type 5 (HAdV-5) was investigated in calves using indirect immunofluorescence microscopy (IIFM ... [more ▼]

Bovine herpesvirus 1 glycoprotein D (gD) gene expression by recombinant replication defective human adenovirus type 5 (HAdV-5) was investigated in calves using indirect immunofluorescence microscopy (IIFM), confocal laser scanning microscopy (CLSM) and RT-PCR. One fold intranasal instillation of HAdV-5-expressing gD in the cattle upper respiratory tract showed a short term expression of at least 5 days, but not 10 days, limited only to epithelial cells localised in the epithelium of the nasal mucosa in one out of six calves. Observed limited gene transfer into well differentiated cattle airway epithelial cells must be taken into consideration in order to enhance transfection efficiency, and consequently the vaccine potential of this vector. [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 ▲]