Oncogenicitiy Comparison of Human Papillomavirus Type 52 E6 Variants

Human papillomavirus (HPV) infection contributes to virtually all cases of cervical cancer, the fourth most common cancer affecting women worldwide. The oncogenicity of HPV is mainly attributable to the E6 and E7 oncoproteins. HPV-52 is the seventh most common HPV type globally, but it has a remarkably high prevalence in East Asia. In previous studies it has been speculated that the oncogenicity might vary among different HPV-52 variants. In the present study, we compared the oncogenicity of E6 derived from the HPV-52 prototype and three commonly found variants, V1 (K93R), V2 (E14D/V92L) and V3 (K93R/N122K), through molecular and phenotypic approaches. We demonstrated that cells containing V1 achieved higher colony formation and showed greater cell migration ability when compared to other variants, but no difference in cell immortalization ability was observed. At the molecular level, the three variants formed complexes with E6-associated protein (E6AP) and p53 as efficiently as the prototype. They degraded p53 and PSD95/Dlg/ZO-1(PDZ) proteins, including MAGI-1c and Dlg, to a similar extent. They also exhibited a similar subcellular localization, and shared a half-life of approximately 45 min. Our findings provide a clearer picture of HPV-52 E6 variant oncogenicity, which is important for further studies aiming to understand the unusually high prevalence of HPV-52 among cervical cancers in East Asia.