Endogenous expression of E1A in human cells enhances the effect of adenovirus E3 on class I major histocompatibility complex antigen expression.
Group C human adenovirus (Ad) serotypes (e.g., Ad type 2 [Ad2] and Ad5) cause persistent infections in humans. One explanation for Ad persistence is an ineffective cytotoxic T-lymphocyte response due to diminished cell surface expression of class I major histocompatibility antigen (MHC Ag) on Ad-infected cells, an effect mediated by the Ad E3 19-kDa glycoprotein (E3 effect). However, we previously reported that, except for the Ad5 E1-transformed human cell line 293, a variety of human lymphoid, epithelial, and fibroblastic cells are resistant to the E3 effect during Ad5 infection (J. M. Routes and J. L. Cook, J. Immunol. 144:2763-2770, 1990). The present study tested the hypothesis that endogenous expression of E1A proteins in 293 cells sensitizes cells to this E3 effect, resulting in an enhanced downregulation of surface class I MHC Ag expression following Ad5 infection. Human epithelial and fibroblastic cells expressing E1A gene products for at least 72 h exhibited an enhanced E3 effect following Ad5 infection that was independent of baseline levels of surface class I MHC Ag expression and of E1A induction of E3 19-kDa glycoprotein expression. There was a direct correlation between the level of endogenous E1A expressed and the magnitude of the E3 effect. We postulate that the in vivo existence of cells stably expressing either E1A proteins or E1A-like activities in the microenvironment of Ad5 infection provides a reservoir of Ad-infected cells that is relatively protected from the virus-specific cytotoxic T-lymphocyte response, thereby favoring Ad persistence in humans.
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
J M
JM
Routes
B A
BA
Metz
J L
JL
Cook
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000276:immunology*; D017503:Adenovirus E3 Proteins / Q000096:biosynthesis / Q000276:immunology*; D000260:Adenoviruses, Human / Q000254:growth & development / Q000276:immunology*; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005805:Genes, MHC Class I / Q000276:immunology*; D006801:Humans
D017500:Adenovirus E1A Proteins; D017503:Adenovirus E3 Proteins