The use of ENU-mutagenesis mouse model to study the role of IL-15 alternative splice variant in the control of herpes simplex virus-1 infection (134.85)

Abstract

Cytokine splice variants generated from alternative splicing of pre-mRNA have been broadly described and are implicated to influence cytokine signaling. Nonetheless, their importance in regulating the immune response remains unclear. The ENU-mutagenized pedigree 191 (P191) generated by the Mouse Mutagenesis Program Core Facility funded by the National Science Council was characterized by its depressed expression of CD44 on CD8 T cells. The mutant gene was linked to chromosome 8 and was mapped to IL-15 mRNA. Infection of P191 mutant mice with HSV-1 via flank skin revealed insufficient control of zosteriform as results of severe and delayed pathological manifestations, increased viral yields and lacking of Gr1+ cell recruitment to the lesional site. Whereas antigen specific CD8 T cells were generated in P191 mutant mice after HSV-1 infection detected with MHC class I tetramer in complex with HSV-1 gB498-505 epitope by flow cytometric analysis, the number was declined later time as opposed to be accumulated as generated in the wild type mice. These results have suggested that expression of IL-15 alternative splice variant could not only have effect ongenerating effective innate immune response in skin but also affect the function and maintenance of CD8 memory cells against HSV-1 infection. However, how the IL-15 splice variant modulates these immune mechanism remains to be clarified.