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Subversion of Host Defense Mechanisms by Adenoviruses

  • Chapter
Viral Proteins Counteracting Host Defenses

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 269))

Abstract

Adenoviruses (Ads) cause acute and persistent infections. Alike the much more complex herpesviruses, Ads encode numerous immunomodulatory functions. About a third of the viral genome is devoted to counteract both the innate and the adaptive antiviral immune response. Immediately upon infection, E1A blocks interferon-induced gene expression and the VA-RNA inhibits interferon-induced PKR activity. At the same time, E1A reprograms the cell for DNA synthesis and induces the intrinsic cellular apoptosis program that is interrupted by E1B/19K and E1B/55K proteins, the latter inhibits p53-mediated apoptosis. Most other viral stealth functions are encoded by a separate transcription units, E3. Several E3 products prevent death receptor-mediated apoptosis. E3/14.7K seems to interfere with the cytolytic and pro-inflammatory activities of TNF while E3/10.4K and 14.5K proteins remove Fas and TRAIL receptors from the cell surface by inducing their degradation in lysosomes. These and other functions that may afect granule-mediated cell death might drastically limit lysis by NK cells and cytotoxic T cells (CTL). Moreover, Ads interfere with recognition of infected cell by CTL. The paradigmatic E3/19K protein subverts antigen presentation by MHC class I molecules by inhibiting their transport to the cell surface. In concert, these viral countermeasures ensure prolonged survival in the infected host and, as a consequence, facilitate transmission. Elucidating the molecular mechanisms of Ad-mediated immune evasion has stimulated corresponding research on other viruses. This knowledge will also be instrumental for designing better vectors for gene therapy and vaccination, and may lead to a more rational treatment of life-threatening Ad infections, e.g. in transplantation patients.

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  1. H.-G. Burgert

    Present address: Department of Biological Sciences, The University of Warwick, CV4 7AL, Coventry, UK

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  1. Max von Pettenkofer-Institut, Lehrstuhl Virologie, Genzentrum der Ludwig-Maximilians-Universität, Feodor-Lynen-Str. 25, 81377, München, Germany

    H.-G. Burgert, Z. Ruzsics, S. Obermeier, A. Hilgendorf, M. Windheim & A. Elsing

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  1. Max von Pettenkofer Institute, University of Munich, Pettenkoferstr. 9a, 80336, Munich, Germany

    Ulrich H. Koszinowski

  2. Robert Koch-Institut, Fachgebiet 1.2 Virale Infektionen, Nordufer 20, 13353, Berlin, Germany

    Hartmut Hengel

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Burgert, HG., Ruzsics, Z., Obermeier, S., Hilgendorf, A., Windheim, M., Elsing, A. (2002). Subversion of Host Defense Mechanisms by Adenoviruses. In: Koszinowski, U.H., Hengel, H. (eds) Viral Proteins Counteracting Host Defenses. Current Topics in Microbiology and Immunology, vol 269. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59421-2_16

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