Mechanistic Contributions of lncRNAs to Cellular Signaling Pathways Crucial to the Lifecycle of Human Papillomaviruses

• Published in: Viruses Vol. 14; no. 11; p. 2439
• Main Authors: Arman, Warda, Munger, Karl
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2022; MDPI
• Subjects: Alphapapillomavirus - genetics; Animals; Antiviral agents; basal cell identity; Cell cycle; Cell differentiation; cellular proliferation; Cellular signal transduction; Cervical cancer; Circular DNA; DNA biosynthesis; DNA damage; DNA repair; DNA viruses; Epithelial cells; epithelial differentiation; Genetic aspects; Genomes; Human papillomavirus; human papillomaviruses; Humans; Life Cycle Stages; Life cycles; long noncoding RNA; MicroRNAs; Non-coding RNA; Offspring; Papillomaviridae; Papillomaviridae - physiology; Papillomavirus infections; Papillomavirus Infections - genetics; Persistent infection; Physiological aspects; Proteins; Regulation; Replication; Review; RNA; RNA, Long Noncoding - genetics; Signal Transduction; Transcription factors; Transcriptomes; Viral infections; viral lifecycle; Virus Replication; United States; long noncoding RNA; human papillomaviruses; viral lifecycle; epithelial differentiation; basal cell identity; cellular proliferation
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14112439

Papillomaviruses are ubiquitous epitheliotropic viruses with double-stranded circular DNA genomes of approximately 8000 base pairs. The viral life cycle is somewhat unusual in that these viruses can establish persistent infections in the mitotically active basal epithelial cells that they initially infect. High-level viral genome replication ("genome amplification"), the expression of capsid proteins, and the formation of infectious progeny are restricted to terminally differentiated cells where genomes are synthesized at replication factories at sites of double-strand DNA breaks. To establish persistent infections, papillomaviruses need to retain the basal cell identity of the initially infected cells and restrain and delay their epithelial differentiation program. To enable high-level viral genome replication, papillomaviruses also need to hold the inherently growth-arrested terminally differentiated cells in a replication-competent state. To provide ample sites for viral genome synthesis, they target the DNA damage and repair machinery. Studies focusing on delineating cellular factors that are targeted by papillomaviruses may aid the development of antivirals. Whilst most of the current research efforts focus on protein targets, the majority of the human transcriptome consists of noncoding RNAs. This review focuses on one specific class of noncoding RNAs, long noncoding RNAs (lncRNAs), and summarizes work on lncRNAs that may regulate the cellular processes that are subverted by papillomavirus to enable persistent infections and progeny synthesis.