CTL recognition of west Nile virus-infected fibroblasts is cell cycle dependent and is associated with virus-induced increases in class I MHC antigen expression.
Confluent and non-confluent mouse embryo fibroblast (CMEF and NCMEF) monolayers were infected with West Nile virus (WNV) for 24 hr, and class I major histocompatibility complex antigen (MHC-I) concentrations measured by flow cytometry (FCM). Concentrations on CMEF increased significantly more than on NCMEF. This was not owing to differences in interferon-beta (IFN-beta)-mediated MHC induction, as the IFN-beta quantity secreted by each infected fibroblast was similar in each culture, and IFN-beta-mediated MHC-I induction on NCMEF was greater than on CMEF. Furthermore, despite neutralization of WNV-induced supernatant IFN-beta, CMEF increased MHC-I expression significantly more than NCMEF. Functionally, WNV-infected CMEF were lysed 10-fold better by WNV-specific and allospecific cytotoxic T cells, than infected NCMEF. FCM demonstrated 76% CMEF and 68% NCMEF distributed in G0/G1. This represented G0 in CMEF, and G1 in NCMEF, confirmed by ribonucleotide reductase M1 subunit labelling, where only 20% CMEF was labelled, compared to 84% NCMEF. The possible implications for antiviral immune responses are discussed.
Department of Anatomy, University of Sydney, New South Wales, Australia.
M W
MW
Douglas
A M
AM
Kesson
N J
NJ
King
D000818:Animals; D002453:Cell Cycle / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D016899:Interferon-beta