a New IFN-Inducible Human Member of the Ly6a Subfamily Expressed by Spleen Cells and Associated with Inflammation and Viral Resistance

Syntenic genomic loci on human chromosome 8 and mouse chromosome 15 (mChr15) code for LY6/Ly6 (lymphocyte Ag 6) family proteins. The 23 murine family genes include eight genes that are flanked by the murine and genes and form an Ly6 subgroup referred to in this article as the Ly6a subfamily gene cluster. , also known as and , is a member of the Ly6a subfamily gene cluster. No genes have been annotated within the syntenic to human locus. We report in this article on , a solitary human gene that is syntenic with the murine Ly6a subfamily gene cluster, and with which it shares a common ancestry. codes for the IFN-inducible GPI-linked LY6S-iso1 protein that contains only 9 of the 10 consensus LY6 cysteine residues and is most highly expressed in a nonclassical spleen cell population. Its expression leads to distinct shifts in patterns of gene expression, particularly of genes coding for inflammatory and immune response proteins, and LY6S-iso1-expressing cells show increased resistance to viral infection. Our findings reveal the presence of a previously unannotated human IFN-stimulated gene, , which has a 1:8 ortholog relationship with the genes of the Ly6a subfamily gene cluster, is most highly expressed in spleen cells of a nonclassical cell lineage, and whose expression induces viral resistance and is associated with an inflammatory phenotype and with the activation of genes that regulate immune responses.