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. 2003 May;77(10):5632-8.
doi: 10.1128/jvi.77.10.5632-5638.2003.

Tmevpg1, a candidate gene for the control of Theiler's virus persistence, could be implicated in the regulation of gamma interferon

Affiliations

Tmevpg1, a candidate gene for the control of Theiler's virus persistence, could be implicated in the regulation of gamma interferon

Soline Vigneau et al. J Virol. 2003 May.

Abstract

The Tmevp3 locus controls the load of Theiler's virus RNA during persistent infection of the mouse central nervous system (CNS). We identified a candidate gene at this locus, Tmevpg1, by using a positional cloning approach. Tmevpg1 and its human ortholog, TMEVPG1, are expressed in the immune system and encode what appears to be a noncoding RNA. They are located in a cluster of cytokine genes that includes the genes for gamma interferon and one or two homolog of interleukin-10. We now report that Tmevpg1 is expressed in CNS-infiltrating immune cells of resistant B10.S mice, but not in those of susceptible SJL/J mice, following inoculation with Theiler's virus. The pattern of expression of Tmevpg1 is the same in B10.S mice and in SJL/J mice congenic for the resistant B10.S haplotype of Tmevp3. Nineteen polymorphisms were identified when the Tmevpg1 genes of B10.S and SJL/J mice were compared. Interestingly, Tmevpg1 is down regulated after in vitro stimulation of murine CD4(+) or CD8(+) splenocytes, whereas Ifng is up regulated. Similar patterns of expression of TMEVPG1 and IFNG were observed in human NK cells and CD4(+) and CD8(+) T lymphocytes. Therefore, Tmevpg1 is a strong candidate gene for the Tmevp3 locus and may be involved in the control of Ifng gene expression.

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Figures

FIG. 1.
FIG. 1.
Expression of the Tmevpg1 gene in mice. Expression of the Tmevpg1 and β-Actin genes in the spleens (A) and thymuses (B) of uninfected SJL/J, B10.S, and C1 and C2 congenic mice and in the brains (C) of SJL/J and B10.S mice at 0, 3, 6, and 9 days p.i. (d.p.i.) with Theiler's virus. Two mice of each strain were studied, one male and one female. +, positive control; −, negative control (water).
FIG. 2.
FIG. 2.
Genotype of the telomeric part of chromosome 10 of SJL/J, B10.S, and C1 and C2 congenic mice. Open squares, regions from the SJL/J parent; solid squares, regions from the B10.S parent; hatched squares, a genetic segment where a crossover occurred. Markers indicating polymorphisms between the SJL/J and B10.S parents are on the left. The lines at the right indicate the positions of the Tmevp2 and Tmevp3 loci. The Tmevpg1 gene is located between the Ifng and D10Mit234 markers. Genetic positions, except for those of the D10Mit74, D10Mit234, and D10Mit14 markers, were obtained from http://www.informatics.jax.org/. cM, centimorgans.
FIG. 3.
FIG. 3.
Polymorphisms in the Tmevpg1 gene sequences of the SJL/J and B10.S strains. The SJL/J and B10.S genomic sequences of the six exons (A) and the 235-bp region of the promoter that is conserved between the mouse and human genomes (B) were compared by using DNA Strider (CEA, Gif-sur-Yvette, France). In panel A, the sequences of the primer pair used to study Tmevpg1 expression are in bold characters. In panel B, the positions are those of the sequence of BAC 13C18.
FIG. 4.
FIG. 4.
Expression of the Tmevpg1 gene in immune cells. (A) Expression of the Tmevpg1 and β-Actin genes in the spinal cords of bone marrow chimeras of SJL/J and B10.S mice at 45 days p.i. with Theiler's virus. B → S, SJL/J mice reconstituted with B10.S bone marrow; B → B, B10.S mice reconstituted with B10.S bone marrow; S → S, SJL/J mice reconstituted with SJL/J bone marrow; S → B, B10.S mice reconstituted with SJL/J bone marrow. Two mice were studied in each case. (B) Expression in B10.S splenocytes. +, positive control; −, negative control (water).
FIG. 5.
FIG. 5.
Genomic organization of the murine Tmevpg1 and Ifng genes on chromosome 10. Solid squares, exons; arrows, 5′-to-3′ orientation of a gene. No gene has been identified between Tmevpg1 and Ifng. This map is based on data from http://www.ensembl.org/Mus_musculus/
FIG. 6.
FIG. 6.
Expression of the murine Tmevpg1 and Ifng genes in CD4+ (A) and CD8+ (B and C) splenocytes. Hours after activation by PMA and ionomycin are indicated. TS, total splenocytes; W, 48 h after removal of PMA and ionomycin and washing; +, positive control; −, negative control (water); IFN-γ, gamma interferon.
FIG. 7.
FIG. 7.
Expression of human TMEVPG1 and IFNG in NK cells (A), CD4+ T lymphocytes (B), and CD8+ T lymphocytes (C). Two and three samples from different healthy volunteers were studied for CD4+ and CD8+ T lymphocytes, respectively. Hours after activation by PMA and ionomycin are indicated. W, 48 h after removal of PMA and ionomycin and washing; +, positive control; −, negative control (water); IFN-γ, gamma interferon.

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