title: Subversion of host defense mechanisms by adenoviruses.
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.
authors.affiliation: Max von Pettenkofer-Institut, Lehrstuhl Virologie, Genzentrum der Ludwig-Maximilians-Universität, Feodor-Lynen-Str. 25, 81377 München, Germany.
authors.forename: H G
authors.initials: HG
authors.lastname: Burgert
authors.forename: Z
authors.initials: Z
authors.lastname: Ruzsics
authors.forename: S
authors.initials: S
authors.lastname: Obermeier
authors.forename: A
authors.initials: A
authors.lastname: Hilgendorf
authors.forename: M
authors.initials: M
authors.lastname: Windheim
authors.forename: A
authors.initials: A
authors.lastname: Elsing
mesh_terms: D000256:Adenoviridae / Q000276:immunology / Q000502:physiology*; D000257:Adenoviridae Infections / Q000276:immunology / Q000821:virology*; D017500:Adenovirus E1A Proteins / Q000502:physiology; D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D015536:Down-Regulation; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons; D007694:Killer Cells, Natural / Q000276:immunology; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic; D014779:Virus Replication
chemical_list: D017500:Adenovirus E1A Proteins; D017503:Adenovirus E3 Proteins; D007372:Interferons