Regulation of HPV transcription

Abstract

Human papillomavirus infection is associated with the development of malignant and benign neoplasms. Approximately 40 viral types can infect the anogenital mucosa and are categorized into high- and low-risk oncogenic human papillomavirus, depending on their association with the development of cervical carcinoma. High-risk human papillomavirus 16 and 18 are detected in 55% and 15% of all invasive cervical squamous cell carcinomas worldwide, respectively. Low-risk human papillomavirus 6 and 11 are responsible for 90% of genital warts and are also associated with the development of recurrent respiratory papillomatosis. Human papillomavirus preferentially infects mitotic active cells of the basal layer from both mucosal and cutaneous epithelium through microabrasions. The viral life cycle synchronizes with the epithelial differentiation program, which may be due, in part, to the binding of differentially expressed cellular transcription factors to the long control region throughout the various epithelial layers. This review aimed to summarize the current knowledge regarding the mechanisms by which viral gene expression is regulated and the influence of human papillomavirus heterogeneity upon this phenomenon. A better understanding of the regulatory mechanisms may elucidate the particularities of human papillomavirus-associated pathogenesis and may provide new tools for antiviral therapy.

The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis

“…Some HPV early gene products such as E1 and E2 are critical regulators of viral DNA transcription and replication and E2 especially contributes to maintaining the intracellular transport and nuclear accumulation of the DNA during infection [17]. Another early viral gene product E4, facilitates viral replication and is implicated in the disruption of cellular cytoskeleton to facilitate the exit of virions from infected keratinocytes [18,19]. E6 and E7 drive most of the cellular events leading to malignant transformation and thus they are considered the major oncogenic proteins of HPV.…”

“…E6 and E7 drive most of the cellular events leading to malignant transformation and thus they are considered the major oncogenic proteins of HPV. E6 product binds mainly to tumor suppressor protein p53 and induces cell cycle arrests in the S phase of the cell cycle and E7 binds and inactivates tumor suppressor pRB resulting in tumorigenesis [19]. E5 interacts with multiple host cell proteins and has been recently recognized as an oncoprotein whose carcinogenic properties include, stimulation of cell proliferation, inhibition of apoptosis induced by death receptors, and the modulation of genes implicated in cell adhesion and immune function [20].…”

Manipulation of Epithelial Differentiation by HPV Oncoproteins

“…For high-risk HPV, E6 and E7 are transcribed as a bicistronic early transcript and splicing of E6 is required for E7 translation [16,17]. In contrast, low-risk genus alpha HPV and genus beta HPV transcribe E6 and E7 from two distinct promoters and do not exhibit the corresponding splice in E6 [18]. Another major splicing event is a differentiation-dependent splice that is required to produce the E1^E4 transcript encoding the E4 protein.…”

The Relationship between Estrogen-Related Signaling and Human Papillomavirus Positive Cancers

“…These ORFs are transcribed from a single DNA strand and can be divided into three functional parts: a largely non-coding region referred to as the long control region (LCR), the early (E) region, and the late (L) region [16]. The LCR contains cis elements that are necessary for the control of viral replication and transcription [17][18][19]. The early region encodes proteins (E1, E2, E4-E7) that are transcribed from an early promoter, and are responsible for the replication and transcription of the viral DNA, as well as structural regulation of the virus, and the principal regulators of viral oncogenesis [16,20].…”