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

Abstract

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.