Nature Immunology
3, 529 - 535 (2002)
Published online: 20 May 2002; | doi:10.1038/ni799
MCMV glycoprotein gp40 confers virus resistance to CD8+
T cells and NK cells in vivoAstrid Krmpoti 1, Dirk H. Busch2, Ivan Bubi1, Friedemann Gebhardt2, Hartmut Hengel3, Milena Hasan1, Anthony A. Scalzo4, Ulrich H. Koszinowski5
& Stipan Jonji11
Department of Histology and Embryology, Faculty of
Medicine, University of Rijeka, Rijeka,
Croatia. 2
Institute of Microbiology, Immunology and Hygiene,
Technical University Munich, Germany. 3
Robert Koch-Institute, Berlin,
Germany. 4
Department of Microbiology, University of Western
Australia, Nedlands, WA, Australia. 5
Max von Pettenkofer Institute,
Munich, Germany.
Correspondence should be addressed to Stipan Jonji jstipan@medri.hrThe 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.
|
