Sensing infection by adenovirus: Toll-like receptor-independent viral DNA recognition signals activation of the interferon regulatory factor 3 master regulator

Marcelo Nociari, Oksana Ocheretina, John W. Schoggins, Erik Falck-Pedersen

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Infection with adenovirus vectors (AdV) results in rapid activation of innate immunity, which serves the dual purpose of stimulating inflammatory antiviral host defenses and the adaptive immune system. Viral recognition by macrophages, dendritic cells, and other cell types requires an ability to sense the presence of a foreign molecular pattern by "pattern recognition receptors." The nature of the adenoviral sensor, the target ligand of the sensor, and the downstream antiviral signaling response triggered by virus infection have not beea defined for this nonenvelopcd double-stranded DNA (dsDNA) virus. We have identified four critical links involved in AdV recognition by murine antigen-presenting cells (APC) and primary lung fibroblasts: (i) viral recognition occurs chiefly via a Toll-like receptor (TLR)-independent nucleic acid-sensing mechanism recognizing the viral dsDNA genome, (ii) the intact viral particle and capsid proteins are required for efficient intracellular delivery of the viral genome, (iii) delivery of the viral genome triggers interferon regulatory factor 3 (IRF3) phosphorylation, and (iv) IRF3 activation is the required dominant antiviral signaling pathway used by APC, whereas the "primary" involvement of NF-κB, mitogen-activated protein kinase, or Akt pathways is less prominent. In this study we provide the first direct evidence that infection by a dsDNA virus stimulates an IRF3-mediated interferon and proinflammatory response through a TLR-independent DNA-sensing mechanism.

Original languageEnglish (US)
Pages (from-to)4145-4157
Number of pages13
JournalJournal of Virology
Volume81
Issue number8
DOIs
StatePublished - Apr 2007

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Interferon Regulatory Factor-3
Adenoviridae Infections
Toll-Like Receptors
Adenoviridae
Antiviral Agents
antigen-presenting cells
Viral Genome
Antigen-Presenting Cells
genome
dsDNA viruses
infection
Pattern Recognition Receptors
viruses
DNA Viruses
DNA
Capsid Proteins
Viral Proteins
Virus Diseases
interferons
dendritic cells

ASJC Scopus subject areas

  • Immunology

Cite this

Sensing infection by adenovirus : Toll-like receptor-independent viral DNA recognition signals activation of the interferon regulatory factor 3 master regulator. / Nociari, Marcelo; Ocheretina, Oksana; Schoggins, John W.; Falck-Pedersen, Erik.

In: Journal of Virology, Vol. 81, No. 8, 04.2007, p. 4145-4157.

Research output: Contribution to journalArticle

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