Lysis by natural killer cells requires viral replication and glycoprotein expression.
Several lines of evidence suggest that natural killer cells (NK) have an important role in antiviral defense. To be thus effective, NK cells have to recognize and cause lysis of virus-infected cells. The mechanism underlying this interaction was investigated in a murine system using vesicular stomatitis virus (VSV). A large number of cell lines was screened to identify a permissive target for VSV infection and the B16 murine melanoma cells were chosen since VSV replicates in these cells without producing cytopathic effects 24 h after infection. Spontaneous lysis of B16 melanoma cells by spleen cells occurred only if the target cells were previously infected with VSV. Treatment of spleen cells with anti NK 1.1 or anti Thy 1.2 plus complement decreased the specific lysis by 50%, therefore, the phenotype of the effector cells in this system corresponds to the NK cell subset. Immunofluorescent staining with polyclonal and monoclonal anti-VSV antibodies demonstrated that the viral glycoprotein G is abundantly expressed on the target cell surface. Treatment of the VSV-infected targets with tunicamycin prevented glycosylation of newly synthesized VSV glycoprotein G on the cell membrane. This treatment abrogated completely NK-mediated killing of the infected B16 melanoma cells. These results indicate that virus replication and membrane expression of glycosylated protein G are essential for recognition and lysis of VSV-infected targets by NK cells.
D000818:Animals; D000954:Antigens, Surface; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D007694:Killer Cells, Natural / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology*; D014779:Virus Replication
D000954:Antigens, Surface; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins