title: Poxvirus infection-associated downregulation of C-type lectin-related-b prevents NK cell inhibition by NK receptor protein-1B.
abstract: Innate immune recognition of virus-infected cells includes NK cell detection of changes to endogenous cell-surface proteins through inhibitory receptors. One such receptor system is the NK cell receptor protein-1B (NKR-P1B) and its ligand C-type lectin-related-b (Clr-b). NKR-P1B and Clr-b are encoded within the NK cell gene complex, a locus that has been linked to strain-dependent differences in susceptibility to infection by poxviruses. In this study, we report the impact of vaccinia virus (VV) and ectromelia virus infection on expression of Clr-b and Clr-b-mediated protection from NK cells. We observed a loss of Clr-b cell-surface protein upon VV and ectromelia virus infection of murine cell lines and bone marrow-derived macrophages. The reduction of Clr-b is more rapid than MHC class I, the prototypic ligand of NK cell inhibitory receptors. Reduction of Clr-b requires active viral infection but not expression of late viral genes, and loss of mRNA appears to lag behind loss of Clr-b surface protein. Clr-b-mediated protection from NK cells is lost following VV infection. Together, these results provide the second example of Clr-b modulation during viral infection and suggest reductions of Clr-b may be involved in sensitizing poxvirus-infected cells to NK cells.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors.forename: Kinola J N
authors.initials: KJ
authors.lastname: Williams
authors.forename: Evan
authors.initials: E
authors.lastname: Wilson
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Davidson
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Aguilar
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: James R
authors.initials: JR
authors.lastname: Carlyle
authors.forename: Deborah N
authors.initials: DN
authors.lastname: Burshtyn
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology* / Q000378:metabolism*
chemical_list: C546928:CLEC1B protein, human; C527212:Klrb1b protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011971:Receptors, Immunologic