Role of HPV16 E1 in cervical carcinogenesis

Abstract

Cervical cancer is the fourth most common cancer in women worldwide. More than 90% of cases are caused by the human papillomavirus (HPV). Vaccines developed only guard against a few HPV types and do not protect people who have already been infected. HPV is a small DNA virus that infects the basal layer of the stratified epithelium of the skin and mucosa through small breaks and replicates as the cells differentiate. The mucosal types of HPV can be classified into low-risk and high-risk groups, based on their association with cancer. Among HPV types in high-risk group, HPV type 16 (HPV-16) is the most common, causing 50% of all cancer cases. HPV infection can occur as transient or persistent infections, based on the ability of immune system to clear the virus. Persistent infection is characterized by the integration of HPV genome. HPV-16 exhibits a different integration pattern, with only 50% reported to be integrated at the carcinoma stage. Replication of the HPV genome depends on protein E1, an ATP-dependent helicase. E1 is essential for the amplification of the viral episome in infected cells. Previous studies have shown that E1 does not only act as a helicase protein but is also involved in recruiting and interacting with other host proteins. E1 has also been deemed to drive host cell proliferation. Recent studies have emphasized the emerging role of HPV E1 in cervical carcinogenesis. In this review, a possible mechanism by which E1 drives cell proliferation and oncogenesis will be discussed.

New insights into Chlamydia pathogenesis: Role of leukemia inhibitory factor

“…Ct infection is also a risk factor for ovarian cancer ( Hosseininasab-Nodoushan et al., 2021 ). While HPV promotes cervical cancer via oncogenic transformation ( Baedyananda et al., 2022 ), Ct may promote cervical cancer and ovarian cancer via aberrant LIF signaling, which has been shown to regulate multiple hallmarks of cancer, including proliferation, metastasis and chemoresistance ( Jones and Jenkins, 2018 ; Jorgensen and de la Puente, 2022 ). LIF also has a significant role in enriching and maintaining cancer stem cells, epithelial to mesenchymal transition, de-differentiation, and re-differentiation of cancer cells ( Halder et al., 2022 ).…”

Designing a Novel Multiepitope Vaccine from the Human Papilloma Virus E1 and E2 Proteins for Indonesia with Immunoinformatics and Molecular Dynamics Approaches

“…Replication of viral DNA also involves the role of E2 proteins. The double-stranded DNA virus cannot replicate without the E1 and E2 proteins, which attach to and unwind the replication origin . For the initiation of viral DNA replication, E1 interacts with E2 to establish the starting point of replication .…”

“…For the initiation of viral DNA replication, E1 interacts with E2 to establish the starting point of replication . Moreover, E1 is highly conserved compared to other HPV proteins, making it an attractive vaccine target . E2 is also an attractive target for therapeutic vaccines as it is expressed at several stages of precancerous lesion development .…”

“…The double-stranded DNA virus cannot replicate without the E1 and E2 proteins, which attach to and unwind the replication origin. 10 For the initiation of viral DNA replication, E1 interacts with E2 to establish the starting point of replication. 11 Moreover, E1 is highly conserved compared to other HPV proteins, making it an attractive vaccine target.…”

“… 11 Moreover, E1 is highly conserved compared to other HPV proteins, making it an attractive vaccine target. 10 E2 is also an attractive target for therapeutic vaccines as it is expressed at several stages of precancerous lesion development. 12 In addition, another study by Ren et alshowed that the E2 protein mediates an alternative pathway to carcinogenesis.…”