Type I interferons and their antiviral function

in Annales de Médecine Vétérinaire (2006), 150(2), 73-107

Type I interferons are part of the innate immune system involved in the first line defense against invasion, replication and spreading of pathogens such as viruses. Through specific membrane or ... [more ▼]

Type I interferons are part of the innate immune system involved in the first line defense against invasion, replication and spreading of pathogens such as viruses. Through specific membrane or intracellular receptors, virus entry induces the expression of type I interferons which stimulates the cells through an autocrine and paracrine manner. Interferons are polypeptides that stimulate cells through membrane receptors. They induce a cascade of events leading to the synthesis of many proteins some of which having specific antiviral properties. The most characterized are the MX proteins, the 2'5' oligoadenylate synthetase/ribonuclease L pathway and the double-stranded RNA-dependent protein kinase R system. Recently, the protein ISG20 has been involved in the specific antiviral function of type I interferons. The interferons act on multiple steps of the viral cycle including penetration, decapsidation, mRNA transcription, protein synthesis, genome replication, assembling and excretion of viral particles. Nowadays, due to their major efficiency, type I interferons are used in therapeutics against some viral infections and cancers. [less ▲]

Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains

in American Journal of Physiology - Lung Cellular and Molecular Physiology (2006), 291

Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 yr of age. It is assumed that host factors influence the severity of the disease presentation and thus the ... [more ▼]

Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 yr of age. It is assumed that host factors influence the severity of the disease presentation and thus the need for hospitalization. As a first step toward the identification of the underlying genes involved, this study was undertaken to establish whether inbred mouse strains differ in susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV, which has been shown to accurately mimic the RSV disease of children. With this purpose in mind, double-chamber plethysmography and carbon monoxide uptake data were collected daily for 7 days after inoculation of PVM in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values reflected the success of viral replication in the lungs and revealed a pattern of continuous variation, with resistant, intermediate, and susceptible strains. The results suggest that SJL (resistant) and 129/Sv (susceptible) strains should be used in crossing experiments aimed at identifying genes controlling pneumovirus replication by the positional cloning approach. Similarly, crossing experiments using BALB/c or C57BL/6 (resistant) and DBA/2 or 129/Sv (susceptible) will allow the identification of the genes involved in the control of pulmonary inflammation during pneumovirus infection. [less ▲]

Anatomy of the Lymphocyte function-associated antigen-1

in Clinical & Applied Immunology Reviews (2006), 6

LFA-1 and associated diseases: the dark side of a receptor

in Clinical & Applied Immunology Reviews (2006), 6

Les interférons de type 1 et leur fonction antivirale

in Annales de Médecine Vétérinaire (2006), 150

Type I interferons are part of the innate immune system involved in the first line defense against invasion, replication and spreading of pathogens such as viruses. Through specific membrane or ... [more ▼]

Type I interferons are part of the innate immune system involved in the first line defense against invasion, replication and spreading of pathogens such as viruses. Through specific membrane or intracellular receptors, virus entry induces the expression of type I interferons which stimulates the cells through an autocrine and paracrine manner. Interferons are polypeptides that stimulate cells through membrane receptors. They induce a cascade of events leading to the synthesis of many proteins some of which having specific antiviral properties. The most characterized are the MX proteins, the 2’5’ oligoadenylate synthetase/ ribonuclease L pathway and the double-stranded RNA-dependent protein kinase R system. Recently, the protein ISG20 has been involved in the specific antiviral function of type I interferons. The interferons act on multiple steps of the viral cycle including penetration, decapsidation, mRNA transcription, protein synthesis, genome replication, assembling and excretion of viral particles. Nowadays, due to their major efficiency, type I interferons are used in therapeutics against some viral infections and cancers. [less ▲]

Flow Cytometry for the follow-up of Trypanosoma evansi infection in a mouse model

Poster (2005, November 18)

Proanthocyanidins, from Ribes Nigrum Leaves, Reduce Endothelial Adhesion Molecules Icam-1 and Vcam-1

in Journal of Inflammation (London, England) (2005), 2

BACKGROUND: The effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, on neutrophil accumulation during inflammatory processes were investigated in vivo and in vitro ... [more ▼]

BACKGROUND: The effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, on neutrophil accumulation during inflammatory processes were investigated in vivo and in vitro. METHODS: In vivo studies were performed using carrageenin-induced pleurisy in rats pre-treated with PACs. Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion molecules (LFA-1, Mac-1 and VLA-4) mobilization in circulating granulocytes were analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were detected by immunohistochemistry on lung sections. In vitro studies were conducted on endothelial LT2 cells, stimulated with TNF-alpha, to evaluate ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment. Data sets were examined by one-way analysis of variance (ANOVA) followed by a Scheffe post-hoc test. RESULTS: Pretreatment of the animals with PACs (10, 30 and 60 mg/kg) inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion molecules mobilization was not down-regulated on granulocytes by PACs. Immunohistochemistry on lung sections showed a decreased production of endothelial cell adhesion molecules. In vitro experiments demonstrated that PACs were able to significantly inhibit ICAM-1 but not IL-8 and VEGF165 mRNA expression. Moreover, VEGF121 mRNA expression was dose-dependently enhanced. CONCLUSION: This study provides evidence to support the anti-inflammatory activity of proanthocyanidins is related to an inhibition of leukocyte infiltration which can be explained at least in part by a down-regulation of endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are capable of modulating TNF-alpha-induced VEGF transcription. [less ▲]

Resistance of paramyxoviridae to type I interferon-induced Bos taurus Mx1 dynamin

in Journal of Interferon & Cytokine Research (2005), 25(4), 192-201

Typical targets of type I interferon (IFN)-induced antiviral Mx proteins known to date have been shown to share a common profile: single-stranded negative-sense RNA viruses. Among them, human MxA is known ... [more ▼]

Typical targets of type I interferon (IFN)-induced antiviral Mx proteins known to date have been shown to share a common profile: single-stranded negative-sense RNA viruses. Among them, human MxA is known to interfere with the replication of measles, human, and bovine parainfluenza-3 viruses (BoPi3V), that is, three members of the Paramyxoviridae family. Recently, bovine Mx1 protein (BoMx1) was included in the group of Mx proteins with authenticated antiviral potential, as it dramatically represses the replication of vesicular stomatitis virus (VSV). As replication in bovine cells of Pi3, respiratory syncytial (RS), and Sendai (Se) viruses, all members of the same family, is known to be reduced on IFN-alpha incorporation into the culture medium, it was hypothesized that the BoMx1 pathway possibly was involved, its antiviral spectrum thus probably extending to Paramyxoviridae. In this study, probing of BoMx1-inhibiting effects was carried out by infecting a transgenic Vero cell line that allows tightly regulated conditional expression of BoMx1 after doxycycline treatment with a wide array of Paramyxoviridae. Expressing and nonexpressing cells displayed similar viability, cytopathic effects (CPEs), and amounts of infectious virus yields, whatever the infecting virus or the multiplicity of infection (moi) imposed. It is, therefore, concluded that BoMx1 does not interfere with Paramyxoviridae. [less ▲]

How Mannheimia haemolytica defeats host defence through a kiss of death mechanism

in Veterinary Research (2005), 36(Mar-Apr), 133-156

Mannheimia haemolytica induced pneumonias are only observed in goats, sheep and cattle. The bacterium produces several virulence factors,whose principal ones are lipopolysaccharide and leukotoxin. The ... [more ▼]

Mannheimia haemolytica induced pneumonias are only observed in goats, sheep and cattle. The bacterium produces several virulence factors,whose principal ones are lipopolysaccharide and leukotoxin. The latter is cytotoxic only for ruminant leukocytes, a phenomenon that is correlated with its ability to bind and interact with the ruminant beta2-integrin Lymphocyte Function-associated Antigen 1. This paper globally reviews all the information available on host-pathogen interactions underlying respiratory mannheimiosis (formerly pasteurellosis), from the stable and the Petri dish to the biochemical cascade of events triggered by the leukotoxin inside ruminant leukocytes. One conclusion can be made: the most widespread cattle respiratory disease with the most important impact on beef production worldwide, is probably due to a tiny ruminant-specific focal variation in the CD18- and/or CD11a-expressing genes. [less ▲]

Molecular characterization of the caprine (Capra hircus) lymphocyte function-associated antigen-1 alpha subunit

in BMC Veterinary Research (2005)

Background: Lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alpha L beta 2) is required for many cellular adhesive interactions during the immune response. Results: The Capra hircus CD11a ... [more ▼]

Background: Lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alpha L beta 2) is required for many cellular adhesive interactions during the immune response. Results: The Capra hircus CD11a-encoding cDNA was sequenced and compared with its human, murine, rat, bovine and ovine counterparts. Despite some focal differences, it shares all the main characteristics of its known mammalian homologues. Conclusion: Therefore, along with the caprine CD18-encoding cDNA, which has been available for a few months, the sequence data revealed here will allow the Capra hircus LFA-1 expression in vitro as a tool to explore the specificities of inflammation in the caprine species. [less ▲]