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Inactivating intracellular antiviral responses during adenovirus infection

Oncogene volume 24, pages 7686–7696 (2005)Cite this article

Abstract

DNA viruses promote cell cycle progression, stimulate unscheduled DNA synthesis, and present the cell with an extraordinary amount of exogenous DNA. These insults elicit vigorous responses mediated by cellular factors that govern cellular homeostasis. To ensure productive infection, adenovirus has developed means to inactivate these intracellular antiviral responses. Among the challenges to the host cell is the viral DNA genome, which is viewed as DNA damage and elicits a cellular response to inhibit replication. Adenovirus therefore encodes proteins that dismantle the cellular DNA damage machinery. Studying virus–host interactions has yielded insights into the molecular functioning of fundamental cellular mechanisms. In addition, it has suggested ways that viral cytotoxicity can be exploited to offer a selective means of restricted growth in tumor cells as a therapy against cancer. In this review, we discuss aspects of the intracellular response that are unique to adenovirus infection and how adenoviral proteins produced from the early region E4 act to neutralize antiviral defenses, with a particular focus on DNA damage signaling.

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Acknowledgements

We thank the members of our labs for lively discussions and their contributions to our work on adenovirus manipulation of cell cycle, protein translation and the DNA damage response. We apologize to our colleagues whose original work may not have been cited due to space constraints. Our work on adenovirus–host cell interactions has been supported in part by grants from the National Institutes of Health (AI43341 and CA97093 to MDW, and AI35589 and CA77342 to DAO).

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  1. Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, 92037, CA, USA

    Matthew D Weitzman

  2. Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, 27157, NC, USA

    David A Ornelles

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Weitzman, M., Ornelles, D. Inactivating intracellular antiviral responses during adenovirus infection. Oncogene 24, 7686–7696 (2005). https://doi.org/10.1038/sj.onc.1209063

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