This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cook, J L Articles by Walker, T A Search for Related Content PubMed PubMed Citation Articles by Cook, J L Articles by Walker, T A

 Previous Article  |  Next Article 

J Virol. 1987 November; 61(11): 3510-3520

Adenovirus E1A gene induction of susceptibility to lysis by natural killer cells and activated macrophages in infected rodent cells.

Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.

ABSTRACT

Rodent cells immortalized by the E1A gene of nononcogenic adenoviruses are susceptible to lysis by natural killer (NK) cells and activated macrophages. This cytolysis-susceptible phenotype may contribute to the rejection of adenovirus-transformed cells by immunocompetent animals. Such increased cytolytic susceptibility has also been observed with infected rodent cells. This infection model provided a means to study the role of E1A gene products in induction of cytolytic susceptibility without cell selection during transformation. Deletion mutations outside of the E1A gene had no effect on adenovirus type 2 (Ad2) or Ad5 induction of cytolytic susceptibility in infected hamster cells, while E1A-minus mutant viruses could not induce this phenotype. E1A mutant viruses that induced expression of either E1A 12S or 13S mRNA in infected cells were competent to induce cytolytic susceptibility. Furthermore, there was a correlation between the accumulation of E1A gene products in Ad5-infected cells and the level of susceptibility of such target cells to lysis by NK cells. The results of coinfection studies indicated that the E1A gene products of highly oncogenic Ad12 could not complement the lack of induction of cytolytic susceptibility by E1A-minus Ad5 virus in infected cells and also could not block induction of this infected-cell phenotype by Ad5. These data suggest that expression of the E1A gene of nononcogenic adenoviruses may cause the elimination of infected cells by the immunologically nonspecific host inflammatory cell response prior to cellular transformation. The lack of induction of this cytolysis-susceptible phenotype by Ad12 E1A may result in an increased persistence of Ad12-infected cells in vivo and may lead to an increased Ad12-transformed cell burden for the host.

This article has been cited by other articles:

• Miura, T. A., Li, H., Morris, K., Ryan, S., Hembre, K., Cook, J. L., Routes, J. M. (2004). Expression of an E1A/E7 Chimeric Protein Sensitizes Tumor Cells to Killing by Activated Macrophages but Not NK Cells. J. Virol. 78: 4646-4654 [Abstract] [Full Text]  
• Cook, J. L., Miura, T. A., Ikle, D. N., Lewis, A. M. Jr., Routes, J. M. (2003). E1A Oncogene-induced Sensitization of Human Tumor Cells to Innate Immune Defenses and Chemotherapy-induced Apoptosis in Vitro and in Vivo. Cancer Res. 63: 3435-3443 [Abstract] [Full Text]  
• Miura, T. A., Morris, K., Ryan, S., Cook, J. L., Routes, J. M. (2003). Adenovirus E1A, Not Human Papillomavirus E7, Sensitizes Tumor Cells to Lysis by Macrophages Through Nitric Oxide- and TNF-{alpha}-Dependent Mechanisms Despite Up-Regulation of 70-kDa Heat Shock Protein. J. Immunol. 170: 4119-4126 [Abstract] [Full Text]  
• Yang, Y., McKerlie, C., Borenstein, S. H., Lu, Z., Schito, M., Chamberlain, J. W., Buchwald, M. (2002). Transgenic Expression in Mouse Lung Reveals Distinct Biological Roles for the Adenovirus Type 5 E1A 243- and 289-Amino-Acid Proteins. J. Virol. 76: 8910-8919 [Abstract] [Full Text]  
• Cook, J. L., Walker, T. A., Worthen, G. S., Radke, J. R. (2002). Role of the E1A Rb-binding domain in repression of the NF-kappa B-dependent defense against tumor necrosis factor-alpha. Proc. Natl. Acad. Sci. USA 99: 9966-9971 [Abstract] [Full Text]  
• Routes, J. M., Ryan, J. C., Ryan, S., Nakamura, M. (2001). MHC class I molecules on adenovirus E1A-expressing tumor cells inhibit NK cell killing but not NK cell-mediated tumor rejection. Int Immunol 13: 1301-1307 [Abstract] [Full Text]  
• Routes, J. M., Ryan, S., Clase, A., Miura, T., Kuhl, A., Potter, T. A., Cook, J. L. (2000). Adenovirus E1A Oncogene Expression in Tumor Cells Enhances Killing by TNF-Related Apoptosis-Inducing Ligand (TRAIL). J. Immunol. 165: 4522-4527 [Abstract] [Full Text]  
• Smith, K., Brown, C. C., Spindler, K. R. (1998). The Role of Mouse Adenovirus Type 1 Early Region 1A in Acute and Persistent Infections in Mice. J. Virol. 72: 5699-5706 [Abstract] [Full Text]  
• Cook, J. L., Krantz, C. K., Routes, B. A. (1996). Role of p300-family proteins in E1A oncogene induction of cytolytic susceptibility and tumor cell rejection. Proc. Natl. Acad. Sci. USA 93: 13985-13990 [Abstract] [Full Text]  
• Javier, R, Raska, K Jr, Shenk, T (1992). Requirement for the adenovirus type 9 E4 region in production of mammary tumors. Science 257: 1267-1271 [Abstract]