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The FANC pathway is activated by adenovirus infection and promotes viral replication-dependent recombination

Gioia Cherubini1, Valeria Naim, Paola Caruso

  • 1University Paris-Sud, UMR8200 CNRS, Institute Gustave Roussy, Villejuif, France.

Nucleic Acids Research
|March 23, 2011
PubMed

Insights

Adenovirus infection hijacks the Fanconi Anemia (FANC) pathway, a DNA repair system, to boost viral replication and recombination. This activation occurs independently of DNA damage, highlighting a novel viral strategy.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Understanding host-virus interactions is crucial for defining viral biology and cellular processes.
  • The Fanconi Anemia (FANC) pathway is involved in DNA damage response and checkpoint control.
  • Alterations in the FANC pathway are associated with Fanconi anemia, a cancer predisposition syndrome.

Purpose of the Study:

  • To identify cellular targets modified by adenovirus (Ad) infection that influence viral outcomes.
  • To investigate the role of the FANC pathway in viral replication and recombination.
  • To elucidate the mechanism of FANC pathway activation during Ad infection.

Main Methods:

  • Analyzing cellular targets modified by adenovirus infection.
  • Investigating the FANC pathway activation in response to adenovirus serotype 5 (Ad5) infection.
  • Utilizing non-replicating Ad and E1A expression to dissect pathway activation triggers.
  • Assessing the role of FANCD2 in viral DNA replication and recombination.

Main Results:

  • Adenovirus infection activates the FANC pathway independently of the classical DNA damage response.
  • Viral DNA presence alone does not induce FANCD2 monoubiquitination but activates DNA damage response markers.
  • Productive viral infection and/or replication are required for FANC pathway activation.
  • FANCD2 activation by Ad5 promotes viral replication, specifically aiding in the recombination process.

Conclusions:

  • Adenovirus 5 (Ad5) infection hijacks the FANC pathway to promote viral replication and recombination.
  • The FANC pathway plays a DNA damage-independent role in facilitating Ad5 recombination.
  • This study reveals a novel cellular mechanism exploited by viruses for their propagation.

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