Faculty Collaboration Database

Adenovirus E1A inhibits IFN-induced resistance to cytolysis by natural killer cells. J Immunol 1993 May 15;150(10):4315-22

Date

05/15/1993

Pubmed ID

7683316

Scopus ID

2-s2.0-0027221548 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

Infection of target cells with cytopathic viruses inhibits IFN induction of cytolytic resistance to NK cell-mediated cytolysis [IFN-mediated cytoprotection (IFN-MCP)]. It has been thought that the virally induced inhibition of IFN-MCP is secondary to the shutdown of cellular macromolecular synthesis that accompanies cytopathic virus infections. Group C, adenovirus serotype 5 (Ad5) infection inhibits both IFN-MCP and cellular protein synthesis. This study determined if the Ad5-induced inhibition of IFN-MCP was independent of adenovirus (Ad) infection and secondary only to the expression of the Ad early region 1A gene (E1A). To test this hypothesis, 4-h NK cytolysis assays were performed on IFN-gamma-treated human cells infected with an Ad5 E1A deletion mutant, dl343, or transfected with the Ad5 E1A gene. IFN-MCP was not inhibited by infection with dl343, despite the production of large amounts of both early (E1B, p55) and late (hexon) Ad proteins. In contrast to E1A-negative, parental cell lines, IFN-MCP was blocked in Ad5 E1A-transfected epithelial and fibroblastic cell lines. Genetic mapping studies within the E1A gene demonstrated that expression of only the first exon of E1A was sufficient to inhibit IFN-MCP. DNA sequence homology of E1A genes between different Ad groups (group A, Ad12; group C, Ad5) is limited almost entirely to three conserved regions located within the first exon of E1A. Because IFN-MCP was also blocked in Ad12 E1A-transfected cell lines, expression of one or more of the E1A-conserved regions may be necessary to inhibit IFN-MCP. In summary, the expression of E1A gene products inhibited IFN-MCP independently of virus infection. E1A's inhibition of IFN-MCP has the net effect of promoting the selective NK cell-mediated clearance of Ad-infected or Ad-transformed human cells.

Author List

Routes JM

Author

John Routes MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenovirus E1A Proteins
Adenoviruses, Human
Cytotoxicity, Immunologic
Exons
Gene Expression
Genes, Viral
Humans
In Vitro Techniques
Interferons
Killer Cells, Natural
Tumor Cells, Cultured
Tumor Virus Infections
Viral Structural Proteins