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Tumor necrosis factor alpha stimulates expression of adenovirus early region 3 proteins: implications for viral persistence
journal contribution
posted on 2023-05-17, 07:42 authored by Heinrich KornerHeinrich Korner, Fritzsche, U, Burgert, HGHuman adenovirus (Ad) can cause persistent infections in humans. Early region 3 (E3) of the virus appears to be implicated in this phenomenon. This transcription unit encodes proteins that interfere in various ways with host cell functions, including (i) cell-surface expression of histocompatibility class I antigens (HLA), (ii) cell-surface expression of the epidermal growth factor receptor (EGF-R), and (iii) the biological activity of tumor necrosis factor α (TNF-α). We transfected the human cell line 293 with the entire E3 region of Ad2 and investigated the influence of the cytokines TNF-α and interferon γ (IFN-γ) on cell-surface expression of HLA class I and the EGF- R. Whereas IFN-γ treatment induced expression of HLA to some extent but not that of the EGF-R, TNF-α treatment augmented the reduction of these cell- surface molecules. Subsequent studies on the mechanism of this effect showed a TNF-α-dependent upregulation of E3 protein (E3/19K) and mRNA. The significance of this phenomenon was confirmed in infection experiments. A dramatic increase in the amount of E3/19K, even after short induction with low doses of TNF-α could be demonstrated. The study provides evidence for an interaction between the immune system and Ad in which the virus takes advantage of an immune mediator to escape immunosurveillance of the host.
History
Publication title
National Academy of Sciences of The United States of America. ProceedingsVolume
89Issue
24Pagination
11857-11861ISSN
0027-8424Department/School
Menzies Institute for Medical ResearchPublisher
Natl Acad SciencesPlace of publication
2101 Constitution Ave Nw, Washington, USA, Dc, 20418Repository Status
- Restricted