PubMed Health⌕ Search

Biomedical subjects

J F Bureau

Publications and source records attributed to J F Bureau.

At least 19 recordsLinked to original sources
PubMed2001

Disruption of differentiated functions during viral infection in vivo. V. Mapping of a locus involved in susceptibility of mice to growth hormone deficiency due to persistent lymphocytic choriomeningitis virus infection.

Lymphocytic choriomeningitis virus (LCMV) Armstrong strain selectively and persistently infects the majority of growth hormone (GH) producing cells in the anterior lobe of pituitary glands of C3H/St mice but negligibly infects GH producing cells of BALB/WEHI mice (Oldstone et al., Virology 142, 175--182, 1985; Oldstone et al., Science 218, 1125--1127, 1982). Although infected GH cells remain free of structural damage, disrupted initiation of GH transcription (Klavinskis and Oldstone, J. Gen. Virol. 68, 1867--1873, 1989; Valsamakis et al., Virology 156, 214--220, 1987) occurs with a resultant decrease in the synthesis of GH, leading to a failure of growth and development (Oldstone et al., Science 218, 1125--1127, 1982). Microsatellite mapping of DNA obtained from 101 individual C3H/St x BALB/WEHI F1 x F1 mice shows that the growth failure correlates with host genes linked (P value 0.0008) on chromosome 17 just outside of the H-2D MHC site between D17 Mit24 and D17 Mit51, a distance of 2.5 cM. The genetic mapping done here excludes alpha-dystroglycan (alpha-DG), a known receptor for LCMV (Cao et al., Science 282, 2079--2081, 1998) in pathogenesis of GH disease, as alpha-DG is encoded in the mouse by a gene residing on chromosome 9 (Yotsumoto et al., Hum. Mol. Genet. 5, 1259--1267, 1996).

Animals↗
PubMed2001

Homology between a 173-kb region from mouse chromosome 10, telomeric to the Ifng locus, and human chromosome 12q15.

We sequenced a 173-kb region of mouse chromosome 10, telomeric to the Ifng locus, and compared it with the human homologous sequence located on chromosome 12q15 using various sequence analysis programs. This region has a low density of genes: one gene was detected in the mouse and the human sequences and a second gene was detected only in the human sequence. The mouse gene and its human orthologue, which are expressed in the immune system at a low level, produce a noncoding mRNA. Nonexpressed sequences show a higher degree of conservation than exons in this genomic region. At least three of these conserved sequences are also conserved in a third mammalian species (sheep or cow).

Animals↗
PubMed2000

Cytokines in genetic susceptibility to multiple sclerosis: a candidate gene approach. French Multiple Sclerosis Genetics Group.

The immune system is involved in the pathophysiology of multiple sclerosis (MS) but the initiating antigen(s) is not yet identified. Since cytokines control both the intensity and the quality of the immune response they may be relevant candidates for the genetic susceptibility to MS. To analyze the contribution of type 1 and type 2 cytokine and cytokine receptor genes in the genetic susceptibility to MS, we have examined, in 116 French MS sibpairs, whether there is significant linkage between MS and 15 cytokine or cytokine receptor genes using 31 highly polymorphic genetic markers. The data were analyzed using the maximum likelihood score and the transmission disequilibrium approaches. None of the candidate genes tested was significantly linked to MS on the whole population. However, after stratification of the analysis on the basis of sharing (or not) of the HLA-DRB1*1501 allele, indication of linkage was found for the IL2-RB gene. These findings suggest that the IL2-RB locus contributes to the genetic susceptibility in a subgroup of MS patients.

Cytokines↗
PubMed2000

H-2D(b-/-) mice are susceptible to persistent infection by Theiler's virus.

H-2(b) mice are resistant to persistent infection of the central nervous system by Theiler's virus. They clear the infection 7 to 10 days after intracranial inoculation. Resistance maps to the H-2D gene and not to the H-2K gene and is associated with a potent antiviral cytotoxic T-lymphocyte (CTL) response. We used H-2(b) mice in which the H-2D or the H-2K gene had been inactivated to dissect the respective roles of these genes in resistance. We report that H-2D(-/-) but not H-2K(-/-) mice were susceptible to persistent infection. Furthermore, whereas H-2K(-/-) mice mounted a vigorous virus-specific CTL response, similar to that of control C57BL/6 mice, the CTL response of H-2D(-/-) mice was nil or minimal. Using target cells transfected with the H-2D(b) or the H-2K(b) gene, we showed that the H-2K-restricted CTL response against the virus was minimal in H-2D(-/-) mice. These results demonstrate that the H-2D(b) and H-2K(b) genes play nonredundant roles in the resistance to this persistent infection.

Animals↗
PubMed1999

The Th1/Th2 balance does not account for the difference of susceptibility of mouse strains to Theiler's virus persistent infection.

Theiler's virus causes a persistent infection with demyelination that is studied as a model for multiple sclerosis. Inbred strains of mice differ in their susceptibility to viral persistence due to both H-2 and non-H-2 genes. A locus with a major effect on persistence has been mapped on chromosome 10, close to the Ifng locus, using a cross between susceptible SJL/J and resistant B10.S mice. We now confirm the existence of this locus using two lines of congenic mice bearing the B10.S Ifng locus on an SJL/J background, and we describe a deletion in the promoter of the Ifng gene of the SJL/J mouse. We studied the expression of IFN-gamma, IL-2, IL-10, and IL-12 in the brains of SJL/J mice, B10.S mice, and the two lines of congenic mice during the first 2 wk following inoculation. We found a greater expression of IFN-gamma and IL-2 mRNA in the brains of B10.S mice compared with those of SJL/J mice. Also, the ratio of IL-12 to IL-10 mRNA levels was higher in B10.S mice. However, the cytokine profiles were the same for the two lines of resistant congenic mice and for susceptible SJL/J mice. Therefore, the difference of Th1/Th2 balance between the B10.S and SJL/J mice is not due to the Ifng locus and does not account for the difference of susceptibility of these mice to persistent infection.

Animals↗
PubMed1999

Two loci, Tmevp2 and Tmevp3, located on the telomeric region of chromosome 10, control the persistence of Theiler's virus in the central nervous system of mice.

Theiler's virus persistently infects the white matter of the spinal cord in susceptible strains of mice. This infection is associated with inflammation and primary demyelination and is studied as a model of multiple sclerosis. The H-2D gene is the major gene controlling viral persistence. However, the SJL/J strain is more susceptible than predicted by its H-2(s) haplotype. An (SJL/J x B10. S)F1 x B10.S backcross was analyzed, and one quantitative trait locus (QTL) was located in the telomeric region of chromosome 10 close to the Ifng locus. Another one was tentatively mapped to the telomeric region of chromosome 18, close to the Mbp locus. We now report the study of 14 congenic lines that carry different segments of these two chromosomes. Although the presence of a QTL on chromosome 18 was not confirmed, two loci controlling viral persistence were identified on chromosome 10 and named Tmevp2 and Tmevp3. Furthermore, the Ifng gene was excluded from the regions containing Tmevp2 and Tmevp3. Analysis of the mode of inheritance of Tmevp2 and Tmevp3 identified an effect of sex, with males being more infected than females.

Analysis of Variance↗
PubMed1999

Viral load and a locus on chromosome 11 affect the late clinical disease caused by Theiler's virus.

Theiler's virus causes a persistent infection and a demyelinating disease of mice which is a model for multiple sclerosis. Susceptibility to viral persistence maps to several loci, including the interferon gamma locus. Inactivating the gene coding for the interferon gamma receptor makes 129/Sv mice susceptible to persistent infection and clinical disease, whereas inactivating the interferon gamma gene makes C57BL/6 mice susceptible to persistent infection but not to clinical disease. This difference in phenotype is due to the difference in genetic background. Clinical disease depends on high viral load and Tmevd5, a locus on chromosome 11. These results have consequences for the identification of viruses which might be implicated in multiple sclerosis.

Animals↗
PubMed1998

Genetics of susceptibility to Theiler's virus infection.

Theiler's virus is a picornavirus of mouse which causes an acute encephalomyelitis followed by a persistent infection of the white matter resulting in chronic inflammation and demyelination. This disease has been studied as a model for multiple sclerosis. Inbred strains of mice are either resistant--they clear the infection after the acute encephalomyelitis--or susceptible to persistent infection and demyelination. Susceptibility is a polygenic trait which has been analyzed using methods of association with "candidate" genes, and linkage analysis after a complete genome scan. The H-2Db gene is responsible for an efficient CTL response which makes some strains resistant. Non H-2 genes responsible for the susceptibility of other strains have been mapped by linkage analysis to the lfng and, possibly, the Mbp loci. The analysis of a set of congenic mice ruled out the possibility that the relevant gene codes for interferon gamma, and showed that the region around lfng probably contains two susceptibility genes. The analysis of mutant mice showed further that the Mbp gene, which codes for the myelin basic protein, has a major effect on viral persistence.

Animals↗
PubMed1998

Chromosome 14 contains determinants that regulate susceptibility to Theiler's virus-induced demyelination in the mouse.

Theiler's murine encephalomyelitis virus causes a chronic demyelinating disease in susceptible strains of mice that is similar to human multiple sclerosis. Several nonmajor histocompatibility complex-linked genes have been implicated as determinants of susceptibility or resistance to either demyelination or virus persistence. In this study, we used linkage analysis of major histocompatibility complex identical H-2d (DBA/2J x B10.D2) F2 intercross mice to identify loci associated with susceptibility to virus-induced demyelinating disease. In a 20-cM region on chromosome 14, we identified four markers, D14Mit54, D14Mit60, D14Mit61, and D14Mit90 that are significantly associated with demyelination. Because two peaks were identified, one near D14Mit54 and one near D14Mit90, it is possible that two loci in this region are involved in controlling demyelination.

Animals↗
PubMed1998

Viruses and multiple sclerosis.

Animal models illustrate how viruses and host genetic factors may interact to cause immune-mediated demyelination. Similar mechanisms may take place in at least some forms of multiple sclerosis, a disease that is histopathologically heterogeneous. No 'multiple sclerosis virus' has been found yet, although recent data on human herpesvirus-6 antigens in multiple sclerosis brain warrant further investigation. Multiple sclerosis associated retrovirus, a recently described retroviral sequence isolated from multiple sclerosis material, is a member of the endogenous retrovirus-9 family. The association between the expression of this virus associated retrovirus and multiple sclerosis is only tentative.

Animals↗
PubMed1997

The infection of mouse by Theiler's virus: from genetics to immunology.

Theiler's virus is a picornavirus of mouse which causes an acute encephalomyelitis followed by a persistent infection of the white matter of the spinal cord with chronic inflammation and demyelination. This late disease is studied as a model for multiple sclerosis. Inbred strains of mice differ in their susceptibility to persistent infection and demyelination. Resistant strains clear the infection after the acute encephalomyelitis. This observation is the basis of genetic studies which we used as a thread for this review. The H-2D locus has a major effect on susceptibility. The H-2Db gene is involved in a fast and intense CTL response which confers resistance. The Tcrb locus is also implicated, although there is no proof that the susceptibility gene in this region codes for the T-cell receptor. A complete screen of the genome uncovered the role of the Ifng locus and led to the demonstration that IFN-gamma limits viral spread in the white matter. The roles of NK cells and B cells in limiting the infection are discussed. CD4+ T cells participate both in protection against the infection and in demyelination. Finally, the effect of non-immune factors in resistance is illustrated by mice with mutations in the MBP or PLP gene.

Animals↗
PubMed1997

The shiverer mutation affects the persistence of Theiler's virus in the central nervous system.

Theiler's virus persists in the white matter of the spinal cord of genetically susceptible mice and causes primary demyelination. The virus persists in macrophages/microglial cells, but also in oligodendrocytes, the myelin-forming cells. Susceptibility/resistance to this chronic infection has been mapped to several loci including one tentatively located in the telomeric region of chromosome 18, close to the myelin basic protein locus (Mbp locus). To determine if the MBP gene influences viral persistence, we inoculated C3H mice bearing the shiverer mutation, a 20-kb deletion in the gene. Whereas control C3H mice were of intermediate susceptibility, C3H mice heterozygous for the mutation were very susceptible, and those homozygous for the mutation were completely resistant. This resistance was not immune mediated. Furthermore, C3H/101H mice homozygous for a point mutation in the gene coding for the proteolipid protein of myelin, the rumpshaker mutation, were resistant. These results strongly support the view that oligodendrocytes are a necessary viral target for the establishment of a persistent infection by Theiler's virus.

Animals↗