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Journal of Virology, January 2007, p. 229-236, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.00997-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Deficient Major Histocompatibility Complex-Linked Innate Murine Cytomegalovirus Immunity in MA/My.L-H2^b Mice and Viral Downregulation of H-2^k Class I Proteins

Xuefang Xie,^1,2 Abhijit Dighe,¹ Patricia Clark,¹ Pearl Sabastian,¹ Sarah Buss,² and Michael G. Brown^1,2*

Department of Internal Medicine,¹ Department of Microbiology, University of Virginia School of Medicine, Charlottesville, Virginia 22908²

Received 15 May 2006/ Accepted 10 October 2006

NK cells are key effectors of innate immunity and host survival during cytomegalovirus (CMV) infection. Innate murine CMV (MCMV) resistance in MA/My mice requires Ly49H/m157-independent H-2^k-linked NK cell control. Here we show that replacement of MA/My H-2^k with C57L H-2^b susceptibility genes led to a remarkable loss of innate virus immunity, though NK gamma interferon was induced in H-2^b and H-2^k strains shortly after infection. Thus, H-2^b genes expressed in C57L or MA/My.L-H2^b are sufficient in alerting NK cells to intrusion but fail to support NK restraint of viral infection. In addition, novel H-2 recombinant strains were produced and utilized in a further refinement of a critical genetic interval controlling innate H-2^k-linked MCMV resistance. Importantly, this analysis excluded the gene interval from K^k class I through class II. The responsible gene(s) therefore resides in an interval spanning D^k class Ia and more-distal major histocompatibility complex (MHC) nonclassical class Ib genes. Recently, the NK activation receptor Ly49P and MHC class I D^k proteins were genetically implicated in MCMV resistance, in part because Ly49P-expressing reporter T cells could specifically bind D^k molecules on MCMV-infected mouse embryonic fibroblasts (MEFs). However, as we found that H-2^k innate resistance differs in the C57L or MA/My backgrounds and because MCMV very efficiently downregulates H-2^k class I proteins in L929 cells and primary MEFs shortly after infection, a Ly49P/D^k model should not fully explain H-2^k-linked MCMV resistance.

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* Corresponding author. Mailing address: Division of Rheumatology, Box 800412, Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908. Phone: (434) 924-5106. Fax: (434) 924-9578. E-mail: mgb4n{at}virginia.edu.

Published ahead of print on 18 October 2006.

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Journal of Virology, January 2007, p. 229-236, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.00997-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

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