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Journal of Virology, May 2003, p. 5632-5638, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5632-5638.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Tmevpg1, a Candidate Gene for the Control of Theiler's Virus Persistence, Could Be Implicated in the Regulation of Gamma Interferon

Soline Vigneau,1 Pierre-Simon Rohrlich,2,3,{dagger} Michel Brahic,1 and Jean-François Bureau1*

Unité des Virus Lents (CNRS URA 1930),1 Unité Immunité Cellulaire Antivirale,2 Institut Pasteur and Hôpital Robert Debré, Paris, France3

Received 11 November 2002/ Accepted 19 February 2003

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.

* Corresponding author. Mailing address: Unité des Virus Lents (CNRS URA 1930), Batiment A. Lwoff, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 140613325. Fax: 33 140613167. E-mail: jfb{at}pasteur.fr.

{dagger} Present address: Hematology Unit, Hôpital Jean Minjoz, 25030 Besançon Cedex, France.

Journal of Virology, May 2003, p. 5632-5638, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5632-5638.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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