MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo

被引:159
作者
Krmpotic, A
Busch, DH
Bubic, I
Gebhardt, F
Hengel, H
Hasan, M
Scalzo, AA
Koszinowski, UH
Jonjic, S [1 ]
机构
[1] Univ Rijeka, Fac Med, Dept Histol & Embryol, Rijeka, Croatia
[2] Tech Univ Munich, Inst Microbiol Immunol & Hyg, D-8000 Munich, Germany
[3] Robert Koch Inst, D-1000 Berlin, Germany
[4] Univ Western Australia, Dept Microbiol, Nedlands, WA 6009, Australia
[5] Max von Pettenkofer Inst, D-8000 Munich, Germany
关键词
D O I
10.1038/ni799
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The susceptibility of certain inbred mouse strains to murine cytomegalovirus (MCMV) is related to their inability to generate a strong natural killer (NK) cell response. We addressed here whether the MCMV susceptibility of the BALB/c strain is due to viral functions that control NK cell activation in a strain-specific manner. MCMV expresses two proteins, gp48 and gp40, that are encoded by the genes m06 and m152, respectively; they down-regulate major histocompatibility complex (MHC) class I expression at the plasma membrane. Using MCMV deletion mutants and revertants, we found that gp40 but not gp48 controls NK cell activation. Absence of gp40 improved antiviral NK cell control in BALB/c, but not C57BL/6, mice. Down-regulation of H-60, the high-affinity ligand for the NKG2D receptor, was the mechanism by which gp40 modulates NK cell activation. Thus, a single herpesvirus protein has a dual function in inhibiting both the adaptive as well as the innate immune response.
引用
收藏
页码:529 / 535
页数:7
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