UNSPECIFIED (2002) Subversion of host defense mechanisms by adenoviruses. [Journal Item]

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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.

Item Type:	Journal Item
Subjects:	Q Science > QR Microbiology > QR180 Immunology Q Science > QR Microbiology
Series Name:	CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY
Journal or Publication Title:	VIRAL PROTEINS COUNTERACTING HOST DEFENSES
Publisher:	SPRINGER-VERLAG BERLIN
ISSN:	0070-217X
Date:	2002
Volume:	269
Number of Pages:	46
Page Range:	pp. 273-318
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/10336

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