Interferon-induced Sus scrofa Mx1 blocks endocytic traffic of incoming influenza A virus particles
; Garigliany, Mutien-Marie ; Cornet, François et al
in Veterinary Research (2010), 41(3), 29
The interferon-induced Mx proteins of vertebrates are dynamin-like GTPases, some isoforms of which can additionally inhibit the life cycle of certain RNA viruses. Here we show that the porcine Mx1 protein ... [more ▼]
The interferon-induced Mx proteins of vertebrates are dynamin-like GTPases, some isoforms of which can additionally inhibit the life cycle of certain RNA viruses. Here we show that the porcine Mx1 protein (poMx1) inhibits replication of influenza A virus and we attempt to identify the step at which the viral life cycle is blocked. In infected cells expressing poMx1, the level of transcripts encoding the viral nucleoprotein is significantly lower than normal, even when secondary transcription is prevented by exposure to cycloheximide. This reveals that a pretranscriptional block participates to the anti-influenza activity. Binding and internalization of incoming virus particles are normal in the presence of poMx1 but centripetal traffic to the late endosomes is interrupted. Surprisingly but decisively, poMx1 significantly alters binding of early endosome autoantigen 1 to early endosomes and/or early endosome size and spatial distribution. This is compatible with impairment of traffic of the endocytic vesicles to the late endosomes. [less ▲]Detailed reference viewed: 59 (27 ULg)
Pathology of influenza virus H5N1 infection in resistant and susceptible laboratory mice.
Garigliany, Mutien-Marie ; ; et al
Conference (2008, September)Detailed reference viewed: 3 (0 ULg)
MX dynamins and the innate resistance opposed to influenza virus.
Garigliany, Mutien-Marie ; ; et al
Conference (2008, March)Detailed reference viewed: 3 (0 ULg)
Allelic and functional characterization of farm animals interferon-dependent MX dynamins for innate resistance to influenza virus.
Garigliany, Mutien-Marie ; Baise, Etienne ; et al
Poster (2008, January)Detailed reference viewed: 6 (0 ULg)
Differential anti-influenza activity among allelic variants at the Sus scrofa Mx1 locus
; ; et al
in Journal of Interferon & Cytokine Research (2007), 27(2), 147-155
A promising way to oppose infectious challenges would be to improve the resistance of the target species through genetic selection. Theoretically, a candidate gene is available against influenza viruses ... [more ▼]
A promising way to oppose infectious challenges would be to improve the resistance of the target species through genetic selection. Theoretically, a candidate gene is available against influenza viruses since a resistance trait was fortuitously discovered in the A2G mouse strain. This trait was demonstrated to be correlated with the expression of a specific isoform of the type I interferon (IFN)-dependent protein MX, an isoform coded by a specific allele at the mouse Mx1 locus. Two allelic polymorphisms were described recently in the Sus scrofa homologous gene. In this study, the frequencies and distribution of both alleles were evaluated among European domestic pig and wild boar populations by PCR-RFLP, and the anti-influenza activity conferred by both MX1 isoforms was evaluated in vitro using transfection of Vero cells followed by flow cytometric determination of the fraction of influenza virus-infected cells among MX-producing and MX-nonproducing cell populations. A significant difference in the anti-influenza activity brought by the two MX1 isoforms was demonstrated, which suggests that a significant improvement of innate resistance of pigs by genetic selection might be feasible provided the differences found here in vitro are epidemiologically relevant in vivo. [less ▲]Detailed reference viewed: 8 (2 ULg)
Genomic structure, promoter analysis, and expression of the porcine (Sus scrofa) Mx1 gene
; ; Broers, Aurore et al
in Immunogenetics (2006), 58
Allelic polymorphisms at the mouse Mx1 locus affect the probability of survival after experimental influenzal disease, raising the possibility that marker-assisted selection using the homologous locus ... [more ▼]
Allelic polymorphisms at the mouse Mx1 locus affect the probability of survival after experimental influenzal disease, raising the possibility that marker-assisted selection using the homologous locus could improve the innate resistance of pigs to natural influenza infections. Several issues need to be resolved before efficient large scale screening of the allelic polymorphism at the porcine (Sus scrofa) Mx1 locus can be implemented. First, the Mx1 genomic structure has to be established and sufficient flanking intronic sequences have to be gathered to enable simple PCR amplification of the coding portions of the gene. Then, a basic knowledge of the promoter region needs to be obtained as an allelic variation there can significantly alter absolute levels and/or tissue-specificity of MX protein expression. The results gathered here show that the porcine Mx1 gene and promoter share the major structural and functional characteristics displayed by their homologs described in cattle, mouse, chicken, and man. The crucial function of the proximal interferon-sensitive response elements motif for gene expression is also demonstrated. The sequence data compiled here will allow an extensive analysis of the polymorphisms present among the widest spectrum possible of porcine breeds with the aim to identify an Mx1 allele providing antiviral resistance. [less ▲]Detailed reference viewed: 32 (8 ULg)