MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo.
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.
Krmpotić
Astrid
A
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Busch
Dirk H
DH
Bubić
Ivan
I
Gebhardt
Friedemann
F
Hengel
Hartmut
H
Hasan
Milena
M
Scalzo
Anthony A
AA
Koszinowski
Ulrich H
UH
Jonjić
Stipan
S
D000818:Animals; D020296:Animals, Congenic; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D003602:Cytotoxicity, Immunologic; D005260:Female; D017353:Gene Deletion; D005814:Genes, Viral; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C082590:UL4 protein, Human cytomegalovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins