Human papillomavirus type 16 E1^E4 protein (HPV-16 E4)

The Human papillomavirus type 16 (HPV-16) E4 protein, primarily expressed as the E1^E4 fusion product, plays a pivotal role in the late stages of the viral life cycle (UniProt P03124). It is the most abundant viral protein in productive lesions, where it accumulates in the cytoplasm and binds to the keratin cytoskeleton (PubMed: 15105543). This interaction leads to the collapse of the keratin network, which is believed to weaken the cornified cell structure and facilitate the release of mature virions from the epithelium (PubMed: 10823895). Beyond its structural impact, E4 induces cell cycle arrest in the G2 phase by interacting with cyclin B/Cdk1 complexes, thereby creating a cellular environment conducive to viral DNA amplification (PubMed: 12533514). Clinically, E4 is a significant biomarker; its presence indicates a productive infection and can help distinguish between low-grade and high-grade cervical intraepithelial neoplasia (CIN) (PubMed: 23027511). Although not yet the primary target of FDA-approved drugs, E4 is a major focus for the development of therapeutic vaccines and diagnostic assays aimed at controlling HPV-related malignancies (PubMed: 28834708). Its high expression levels and specific role in viral egress make it an attractive target for interventions designed to interrupt the transmission cycle of the virus.

Other names

E1--E4E1^E4HPV16 E4Protein E4

Disruption of the host keratin network to facilitate virion egress and induction of G2/M cell cycle arrest to support viral DNA replication.