Year: 2026
Type: article
Abstract: Human papillomavirus type 16 (HPV16) persistence relies on early viral mechanisms that synchronize oncogenic signaling with immune evasion, with the E5 oncoprotein serving as a central regulator of the viral cycle and the initiation of cell transformation. This review integrates current evidence on how E5 reconfigures host cell dynamics: first, by hijacking signaling pathways such as EGFR, MAPK/ERK, and PI3K/AKT to drive keratinocyte proliferation and survival; and second, by organizing a multi-step immune evasion strategy. We detail how E5 suppresses innate antiviral responses, specifically by repressing IFN-κ and IFN-β via interference with IRF1, TGF-β/SMAD, STING, and MAVS signaling. Simultaneously, E5 interferes with the adaptive immunity by disrupting MHC-I trafficking and impairing MHC-II maturation. Furthermore, preclinical studies utilizing various vaccine platforms targeting HPV16 E5 have demonstrated the capacity to reduce tumor burden and significantly increase survival rates. By integrating these molecular and immunological checkpoints, we highlight the role of E5 in sustaining viral persistence and underscore its potential as a high-value target for next-generation immunotherapeutic and vaccine-based strategies.
DOI: 10.3390/ijms27041985
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7130505831