Pseudotyped GFP HPV51

Papillomaviruses are ubiquitous DNA viruses that infect the skin and mucous membranes of animals and humans. The virus can be transmitted through direct physical contact and does not usually cause noticeable illness. In humans, low-risk types of human papillomavirus (HPV) can cause benign warts. High-risk HPV is the leading cause of cervical cancer, as well as several anogenital cancers and squamous cell carcinomas of the head and neck, the most common of which are HPV16 and HPV18.

Following HPV infection, the expression of HPV genes and the viral life cycle correlate with the differentiation process of the epithelium. Viral genome replication in the undifferentiated basal layer is initiated by HPV proteins E1 and E2. The DNA-binding protein E2 recruits helicase E1 to the viral replication origin and also tethers the viral episomes to the host chromatin to symmetrically distribute the replicated episomes between the two daughter cells. In the mid-epithelium, high expression of E6 and E7 oncogenes leads to the re-entry of differentiated keratinocytes into the cell cycle, thereby inducing proliferation. When the HPV genome is amplified to approximately 100-200 episome copies per cell, E2 negatively regulates early genes, including oncogenes E6 and E7, by binding to the viral non-coding long control region (LCR) upstream of the early promoter, thus preventing transcription factors and the transcription start complex from binding to this regulatory region. When E2 binds to the early promoter and down-regulates the early genes, the viral transcript alters its splicing thereby favoring the initiation of the late differentiation genes E4, L1 and L2, a behavior that triggers the final differentiation of keratinocytes. Late genes L1 and L2 can form the capsid proteins of the virion, which encapsulate viral DNA during viral release and reinfection, and the packaged virus is released upon cell death.

Figure 1. The evolution of HPV infection, to CIN, to invasive cervical cancer (ICC)
(Source: Porter VL, et al. 2022)

HPV infection does not lead to cancer immediately; instead, it takes a long period of persistent infection to induce cervical cancer. This feature also makes it possible to effectively screen for cervical cancer. Cervical cytology screening programmes have significantly reduced mortality and morbidity over the past decades. However, it is not yet possible to accurately predict which of the pre-cancerous lesions detected by screening will invade healthy tissue. In addition, most cervical intraepithelial neoplasia grade 3 (CIN3) precancerous lesions (as well as many CIN2 precancerous lesions) were treated in the screened population, which has led to overtreatment.

Pseudotyped GFP Human papillomavirus 51
Pseudotyped GFP Human papillomavirus type 51