E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells.
Adenovirus (Ad) infection and E1A transfection were used to model changes in susceptibility to NK cell killing caused by transient vs stable E1A expression in human cells. Only stably transfected target cells exhibited cytolytic susceptibility, despite expression of equivalent levels of E1A proteins in Ad-infected targets. The inability of E1A gene products to induce cytolytic susceptibility during infection was not explained by an inhibitory effect of viral infection on otherwise susceptible target cells or by viral gene effects on class I MHC antigen expression on target cells. This differential effect of E1A expression on the cytolytic phenotypes of infected and stably transfected human cells suggests that human NK cells provide an effective immunologic barrier against the in vivo survival and neoplastic progression of E1A-immortalized cells that may emerge from the reservoir of persistently infected cells in the human host.
Routes
J M
JM
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Cook
J L
JL
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D017456:Adenovirus Early Proteins / Q000235:genetics / Q000276:immunology; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015870:Gene Expression; D005814:Genes, Viral; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D009154:Mutation; D014162:Transfection; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D017456:Adenovirus Early Proteins; D015395:Histocompatibility Antigens Class I