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Published on: March 8, 2012
Human papillomavirus 16 E2 blocks cellular senescence in response to activation of the DNA damage response
Christian T Fontan1, Apurva T Prabhakar1, Xu Wang1
1Virginia Commonwealth University (VCU), Philips Institute for Oral Health Research, School of Dentistry, Richmond, Virginia, USA.
Abstract:
Following infection by HPV16, the viral proteins E1 and E2 induce viral genome replication in association with host factors. Here we demonstrate that E2 also plays a role in promoting short-term cellular proliferation in the presence of an active DDR. Cisplatin treatment of E2 expressing cells results in short-term proliferation likely due to a block of cellular senescence and apoptosis. However, long-term growth of E2 expressing cells following cisplatin treatment is attenuated due to an accumulation of DNA damage. We discuss a possible role for this E2 function during the viral life cycle. It is also notable that E2 expressing HPV16 positive cancers have a better clinical outcome than non-E2 expressing tumors. While there are a variety of reasons for the better outcome of patients with E2 expressing tumors, this report suggests that E2 regulation of the DNA damage response may be a contributory factor.
Insights
The HPV16 E2 protein promotes short-term cell proliferation during DNA damage but leads to long-term growth attenuation. E2
Area of Science:
- Molecular Biology
- Virology
- Cancer Research
Background:
- Human papillomavirus type 16 (HPV16) infection involves viral proteins E1 and E2.
- These proteins are crucial for viral genome replication, interacting with host cellular machinery.
Purpose of the Study:
- To investigate the role of HPV16 E2 protein in cellular proliferation and DNA damage response.
- To explore the implications of E2's function in HPV16-positive cancers and patient outcomes.
Main Methods:
- Studied the effect of HPV16 E2 expression on cellular proliferation under cisplatin treatment (inducing DNA damage).
- Assessed cellular senescence, apoptosis, and DNA damage accumulation in E2-expressing cells.
Main Results:
- HPV16 E2 promotes short-term cellular proliferation, potentially by inhibiting senescence and apoptosis following DNA damage.
- Long-term growth of E2-expressing cells is hindered by accumulating DNA damage.
- E2-expressing HPV16-positive tumors show better clinical outcomes compared to non-E2 expressing tumors.
Conclusions:
- HPV16 E2 protein modulates the DNA damage response, influencing both short-term proliferation and long-term cell fate.
- E2's regulation of DNA damage response may contribute to the improved clinical outcomes observed in HPV16-positive cancers expressing E2.
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