Molecular genetic characterization of the distal NKC recombination hotspot and putative murine CMV resistance control locus

Anthony A. Scalzo, Roy Wheat, Chad Dubbelde, Laurie Stone, Patricia Clark, Ying Du, Naomi Dong, Janis Stoll, Wayne M. Yokoyama, Michael G. Brown

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 MrcB6 was not required for MCMV resistance nor could it directly complement the Ly49BALB 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 MrcB6 in virus resistance is excluded in the novel mice.

Original languageEnglish
Pages (from-to)370-378
Number of pages9
JournalImmunogenetics
Volume55
Issue number6
DOIs
StatePublished - Sep 1 2003

Keywords

  • G-protein coupled receptors
  • Natural killer gene complex
  • Recombination hotspot
  • Viral immunity

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