Subversion of Host Defense Mechanisms by Adenoviruses

Curr Top Microbiol Immunol. 2002;269:273-318. doi: 10.1007/978-3-642-59421-2_16.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenoviridae / immunology
  • Adenoviridae / physiology*
  • Adenoviridae Infections / immunology
  • Adenoviridae Infections / virology*
  • Adenovirus E1A Proteins / physiology
  • Adenovirus E3 Proteins / genetics
  • Adenovirus E3 Proteins / physiology
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Down-Regulation
  • Humans
  • Immunity, Innate
  • Interferons
  • Killer Cells, Natural / immunology
  • Molecular Sequence Data
  • Sequence Alignment
  • T-Lymphocytes, Cytotoxic
  • Virus Replication

Substances

  • Adenovirus E1A Proteins
  • Adenovirus E3 Proteins
  • Interferons