β-HPV 8E6 combined with TERT expression promotes long-term proliferation and genome instability after cytokinesis failure

Abstract

Human papillomavirus (HPV) is a family of viruses divided into five genera: alpha, beta, gamma, mu, and nu. There is an ongoing discussion about whether beta genus HPVs (β-HPVs) contribute to cutaneous squamous cell carcinoma (cSCC). The data presented here add to this conversation by determining how a β-HPV E6 protein (β-HPV 8E6) alters the cellular response to cytokinesis failure. Specifically, cells were observed after cytokinesis failure was induced by dihydrocytochalasin B (H2CB). β-HPV 8E6 attenuated the immediate toxicity associated with H2CB but did not promote long-term proliferation after H2CB. Immortalization by telomerase reverse transcriptase (TERT) activation also rarely allowed cells to sustain proliferation after H2CB exposure. In contrast, TERT expression combined with β-HPV 8E6 expression allowed cells to proliferate for months following cytokinesis failure. However, this continued proliferation comes with genome destabilizing consequences. Cells that survived H2CB-induced cytokinesis failure suffered from changes in ploidy.