Ly49h is necessary for genetic resistance to murine cytomegalovirus

Tammy P. Cheng, Anthony R. French, Beatrice F.M. Plougastel, Jeanette T. Pingel, Michael M. Orihuela, Mark L. Buller, Wayne M. Yokoyama

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Natural killer (NK) cells play critical roles in antiviral immunity. While the importance of effector mechanisms such as interferons has been demonstrated through knockout mice, specific mechanisms of how viruses are recognized and controlled by NK cells are less well defined. Previous genetic studies have mapped the resistance genes for murine cytomegalovirus (MCMV), herpes simplex virus-1 (HSV-1), and ectromelia virus to the NK gene complex on murine chromosome 6, a region containing the polymorphic Ly49 and Nkrp1 families. Genetic resistance to MCMV in C57BL/6 has been attributed to Ly49H, an activation receptor, through susceptibility of the recombinant inbred strain BXD-8 that lacks Ly49h (also known as Klra8) but derived about half of its genome from its DBA/2 progenitor. However, it remained possible that epigenetic effects could account for the MCMV phenotype in BXD-8 mice. Herein, we report the generation of a novel congenic murine strain, B6.BXD8-Klra8 Cmv1-del /Wum, on the C57BL/6 genetic background to evaluate the effect of deletion of a single NK activation receptor, Ly49H. Deletion of Ly49H rendered mice much more susceptible to MCMV infection. This increase in susceptibility did not appear to be a result of a difference in NK cell expansion or interferon-γ (IFN-γ) production between the C57BL/6 and the B6.BXD8 strains. On the other hand, the deletion of Ly49h did not otherwise affect NK cell maturation or Ly49D expression and had no effect on susceptibility to HSV-1 or ectromelia virus. In conclusion, Ly49h is necessary for genetic resistance to MCMV, but not HSV-1 or ectromelia virus.

Original languageEnglish
Pages (from-to)565-573
Number of pages9
JournalImmunogenetics
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2008

Keywords

  • Cmv1
  • Cytomegalovirus
  • Ly49H
  • MCMV
  • Natural killer cells

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