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.