Requisite H2~k Role in NK Cell-Mediated Resistance in Acute Murine Cytomegalovirus-Infected MA/My Mice

摘要

Human CMY infections are a major health risk in patients with dysfunctional or compromised immunity,especially in patients with NK cell deficiencies,as these are frequently associated with high morbidity and mortality.In experimental murine CMV(MCMV)infections,Ly49H activation receptors on C57BL/6(B6)NK cells engage m157 viral ligands on MCMV-infected cells and initiate dominant virus control.In this study,we report that MCMV resistance in MA/My relies on Ly49H-independent NK cell-mediated control of MCMV infection as NK cells in these mice do not bind anti-Ly49H mAb or soluble ml57 viral ligands.We genetically compared MA/My resistance with MCMV susceptibility in genealogically and NK gene complex-Ly49 haplotype-related C57L mice.We found that MCMV resistance strongly associated with polymorphic H2~k-linked genes,including MHC and non-MHC locations by analysis of backcross and intercross progeny.The H2~b haplotype most frequently,but not absolutely,correlated with MCMV susceptibility,thus confirming a role for non-MHC genes in MCMV control.We also demonstrate a definite role for NK cells in H2~k-type MCMV resistance because their removal from C57L.M-H2k mice before MCMV infection diminished immunity.NK gene complex-linked polymorphisms,however,did not significantly influence MCMV control.Taken together,effective NK cell-mediated MCMV control in this genetic system required polymorphic H2~k genes without need of Ly49H-ml57 interactions.