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Human papillomavirus (HPV) origin-binding protein associates with mitotic spindles to enable viral DNA partitioning

Brian A Van Tine1, Luan D Dao, Shwu-Yuan Wu

  • 1Department of Molecular Pathology, University of Alabama at Birmingham, 1918 University Boulevard, Birmingham, AL 35294-0005, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 17, 2004
PubMed

Insights

Human papillomaviruses (HPVs) persist by partitioning their DNA as minichromosomes. The viral E2 protein binds to mitotic spindles, ensuring stable DNA inheritance in cycling cells.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Human papillomaviruses (HPVs) are known to establish persistent infections.
  • The mechanism by which extrachromosomal HPV DNA is maintained in replicating cells remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of extrachromosomal HPV DNA persistence in cycling cells.
  • To investigate the role of the viral E2 protein in HPV DNA segregation during cell division.

Main Methods:

  • Co-immunoprecipitation assays to detect interactions between the HPV E2 protein and cellular spindle components.
  • Analysis of HPV DNA partitioning during mitosis.
  • Domain mapping of the HPV E2 protein to identify regions responsible for spindle association.

Main Results:

  • Extrachromosomal HPV DNA was shown to partition as minichromosomes during cell division.
  • The viral E2 protein was found to associate with mitotic spindles.
  • Alpha-, beta-, and gamma-tubulins were co-immunoprecipitated with a tagged E2 protein.
  • Both the N-terminal and C-terminal domains of E2 independently associated with mitotic spindles.

Conclusions:

  • The association of the HPV E2 protein with mitotic spindles is a key mechanism for the stable inheritance of viral DNA in proliferating cells.
  • This E2-spindle interaction facilitates the long-term persistence of HPVs.
  • The findings have implications for understanding HPV-associated oncogenesis.

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