Scalzo Anthony A, Wheat Roy, Dubbelde Chad, Stone Laurie, Clark Patricia, Du Ying, Dong Naomi, Stoll Janis, Yokoyama Wayne M, Brown Michael G
Department of Microbiology, University of Western Australia, 6907 Nedlands, Western Australia, Australia.
Immunogenetics. 2003 Sep;55(6):370-8. doi: 10.1007/s00251-003-0591-8. Epub 2003 Aug 13.
The NK gene complex (NKC) controls murine cytomegalovirus (MCMV) immunity through Cmv1-dependent natural killer (NK) cell responses. Ly49H expression correlates with Cmv1 phenotypes in different inbred strains, is required for MCMV resistance in C57BL/6 (B6) mice, and its interaction with the MCMV encoded m157 protein leads to NK cell-mediated destruction of virus-infected cells. However, genetic mapping studies have previously indicated that Cmv1 should reside in the D6Wum9-16 NKC interval, distal to Ly49h. Since these data suggested that multiple NKC-linked loci could regulate viral immunity, a putative MCMV resistance control ( Mrc) locus was pinpointed to within the D6Wum9-16 interval on a NKC-aligned bacterial artificial chromosome (BAC). Sequence analysis of BAC 151 revealed several novel G-protein coupled receptor genes, an HMG-1 remnant and many additional polymorphic microsatellites that were useful in determining the minimal genetic interval for the Mrc locus. Moreover, comparison of B6, BALB/c, A/J and recombinant Mrc alleles restricted the genetic interval to approximately 470 bp and showed that it was also a hotspot for recombination. MCMV challenge of novel NKC recombinant mice demonstrated that Mrc(B6) was not required for MCMV resistance nor could it directly complement the Ly49(BALB) haplotype to rescue MCMV susceptibility. Taken together, these data show that while Mrc apparently guides recombination, Ly49H expression is sufficient for MCMV resistance in B6 mice. A direct role for Mrc(B6) in virus resistance is excluded in the novel mice.
NK基因复合体（NKC）通过依赖Cmv1的自然杀伤（NK）细胞反应来控制小鼠巨细胞病毒（MCMV）免疫。Ly49H的表达与不同近交系中的Cmv1表型相关，是C57BL/6（B6）小鼠抵抗MCMV所必需的，并且它与MCMV编码的m157蛋白的相互作用导致NK细胞介导的病毒感染细胞的破坏。然而，先前的遗传定位研究表明，Cmv1应该位于Ly49h远端的D6Wum9 - 16 NKC区间内。由于这些数据表明多个与NKC连锁的基因座可能调节病毒免疫，因此在与NKC对齐的细菌人工染色体（BAC）上，将一个假定的MCMV抗性控制（Mrc）基因座定位到D6Wum9 - 16区间内。BAC 151的序列分析揭示了几个新的G蛋白偶联受体基因、一个HMG - 1残余物以及许多其他多态性微卫星，这些对于确定Mrc基因座的最小遗传区间很有用。此外，对B6、BALB/c、A/J和重组Mrc等位基因的比较将遗传区间限制在约470 bp，并表明它也是一个重组热点。对新型NKC重组小鼠进行MCMV攻击表明，Mrc（B6）对于MCMV抗性不是必需的，也不能直接补充Ly49（BALB）单倍型以挽救MCMV易感性。综上所述，这些数据表明，虽然Mrc显然指导重组，但Ly49H的表达足以使B6小鼠抵抗MCMV。在新型小鼠中排除了Mrc（B6）在病毒抗性中的直接作用。
