Interaction of Adenovirus E1A with the HHV8 Promoter of Latent Genes: E1A Proteins are Able to Activate the HHV-8 LANAp in MV3 Reporter Cells



Karin Koehler-Hansner1, Ornella Flore2, Bertram Opalka 1, 4, Ulrich R Hengge*, 3
1 Department of Internal Medicine (Cancer Research), University of Duisburg-Essen Medical School, Essen, Hufelandstrasse 55, D-45122 Essen, Germany
2 Department of Microbiology, New York University Medical School, 550 First Avenue, New York, NY 10016, USA
3 Department of Dermatology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Duesseldorf, Germany
4 at present: Department of Hematology, University of Duisburg-Essen Medical School, Essen, Hufelandstrasse 55, D-45122 Essen, Germany


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© Koehler-Hansner et al.; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/license/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Department of Dermatology, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Duesseldorf, Germany; Tel: +49-(0)211-811-8066; Fax: +49-(0)211-811-8830; E-mail: ulrich.hengge@uni-duesseldorf.de


Abstract

Human herpesvirus 8 (HHV-8) is associated with Kaposi’s sarcoma, body cavity-based lymphoma, and Castleman’s disease. Adenoviral (Ad) E1A proteins regulate the activity of cellular and viral promoters/enhancers and transcription factors and can suppress tumorigenicity of human cancers. As (i) HHV-8 and Ad may co-exist in immunocompromised patients and (ii) E1A might be considered as therapeutic transgene for HHV-8-associated neoplasms we investigated whether the promoter of the latency-associated nuclear antigen (LANAp) controlling expression of vCyclin, vFLIP, and LANA proteins required for latent type infection is regulated by E1A. Transfection experiments in MV3 melanoma cells revealed activation of the LANAp by Ad5 E1A constructs containing an intact N terminus (aa 1-119). In particular, an Ad12 E1A mutant, Spm2, lacking six consecutive alanine residues in the “spacer” region activated the HHV-8 promoter about 15-fold compared to vector controls. In summary, we report the activation of the LANAp by E1A as a novel interaction of E1A with a viral promoter. These data may have relevance for the management of viral infections in immunocompromised patients. A role for E1A as a therapeutic in this context remains to be defined.