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Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells
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Adenovirus type 5 E4orf3 protein targets the Mre11 complex to cytoplasmic aggresomes

Felipe D Araujo1, Travis H Stracker, Christian T Carson

  • 1Laboratory of Genetics, Salk Institute for Biological Studies, San Diego, CA 92186-5800, USA.

Journal of Virology
|August 17, 2005
PubMed

Insights

Adenovirus E4orf3 protein redirects the Mre11 DNA repair complex to aggresomes, preventing viral DNA concatemer formation. This mechanism may inactivate the cellular repair complex during adenovirus infection.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Virus infections significantly alter host cell structure and function.
  • Adenovirus serotype 5 (Ad5) E4orf3 protein is crucial for viral replication and protein synthesis.
  • Cellular DNA repair factors, including the Mre11/Rad50/Nbs1 complex, are involved in adenovirus DNA replication.

Purpose of the Study:

  • To investigate the role of Ad5 E4orf3 protein in the cellular redistribution of the Mre11 complex.
  • To elucidate the mechanism by which E4orf3 affects DNA repair factors during adenovirus infection.

Main Methods:

  • Immunofluorescence microscopy to observe colocalization of E4orf3 and Mre11 complex components.
  • Analysis of Mre11 complex rearrangement in the absence of Nbs1 and PML nuclear bodies.
  • Investigation of microtubule cytoskeleton involvement in cytoplasmic accumulation.
  • Characterization of cytoplasmic inclusions as aggresomes.

Main Results:

  • E4orf3 colocalizes with Mre11 complex components in nuclear tracks and cytoplasmic accumulations.
  • E4orf3-induced Mre11/Rad50 rearrangement is independent of Nbs1 and PML nuclear bodies.
  • Cytoplasmic inclusions form juxtanuclear aggresomes at the centrosome, requiring intact microtubules.
  • E4orf3 alters Mre11 complex solubility and targets it to aggresomes.

Conclusions:

  • Ad5 E4orf3 protein targets the Mre11 DNA repair complex to aggresomes.
  • This targeting mechanism likely contributes to the inactivation of the cellular repair complex during adenovirus infection.
  • E4orf3 plays a role in modulating host cell DNA repair pathways for viral propagation.

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