The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation

• Published in: Journal of general virology Vol. 102; no. 3
• Main Authors: Scarth, James A., Patterson, Molly R., Morgan, Ethan L., Macdonald, Andrew
• Format: Journal Article
• Language: English
• Published: England Microbiology Society 01.03.2021
• Subjects: Alphapapillomavirus - genetics; Alphapapillomavirus - pathogenicity; Alphapapillomavirus - physiology; Apoptosis; Carcinogenesis; Cell Cycle Checkpoints; Cell Differentiation; Cell Proliferation; Cell Transformation, Viral; Cellular Reprogramming; Epigenesis, Genetic; Genome, Viral; Humans; Immune Evasion; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - metabolism; Papillomavirus Infections - virology; PDZ Domains; Review; RNA, Untranslated - genetics; Signal Transduction; Virus Replication; cancer; keratinocyte; oncoprotein; signalling; HPV
• ISSN: 0022-1317; 1465-2099; 1465-2099
• DOI: 10.1099/jgv.0.001540

Persistent infection with high-risk human papillomaviruses (HR-HPVs) is the causal factor in over 99 % of cervical cancer cases, and a significant proportion of oropharyngeal and anogenital cancers. The key drivers of HPV-mediated transformation are the oncoproteins E5, E6 and E7. Together, they act to prolong cell-cycle progression, delay differentiation and inhibit apoptosis in the host keratinocyte cell in order to generate an environment permissive for viral replication. The oncoproteins also have key roles in mediating evasion of the host immune response, enabling infection to persist. Moreover, prolonged infection within the cellular environment established by the HR-HPV oncoproteins can lead to the acquisition of host genetic mutations, eventually culminating in transformation to malignancy. In this review, we outline the many ways in which the HR-HPV oncoproteins manipulate the host cellular environment, focusing on how these activities can contribute to carcinogenesis.