Epstein-Barr virus protein enhances cancer gene activity in HPV-positive cervical cells

A new research paper was published in Volume 16 of Genes & Cancer on August 6, 2025, titled "Epstein-Barr virus nuclear antigen 1 upregulates Derlin1 and PSMD10 expression in HeLa cells."

In this study, led by first authors Amir Hossein Alipour and Seyed Mohammad Ali Hashemi, along with corresponding author Jamal Sarvari from Shiraz University of Medical Sciences, the researchers investigated how a protein from the Epstein-Barr virus (EBV) influences gene activity in cervical cancer cells. They found that EBV nuclear antigen 1 (EBNA1) significantly increases the expression of two genes-Derlin1 and PSMD10-both of which are known to play roles in cancer development. These results suggest a potential mechanism by which EBV may contribute to the progression of cervical cancer, particularly in patients who are also infected with human papillomavirus (HPV).

Cervical cancer is among the most common cancers affecting women globally. While high-risk HPV types are the primary cause, increasing evidence suggests that other viruses like EBV may act as partners, further driving the disease. EBV is already known for its involvement in several cancers, including nasopharyngeal carcinoma and gastric cancer. This study aimed to clarify whether EBNA1 can influence gene activity in HPV-positive cervical cancer cells.

Using the HeLa cervical cancer cell line, which contains HPV-18, the researchers introduced the EBNA1 gene and analyzed the expression of four specific genes: Derlin1, PSMD10, ZEB1, and CNN3. They observed that EBNA1 caused a three-fold increase in Derlin1 expression and a two-fold increase in PSMD10 expression. These two genes are associated with enhanced cancer cell survival, proliferation, and treatment resistance. The changes observed in ZEB1 and CNN3 were not statistically significant.

"The results demonstrated that HeLa cells transfected with the EBNA1 plasmid exhibited significantly increased expression levels of Derlin1 (p = 0.028) and PSMD10 (p = 0.028) genes compared to cells transfected with the control plasmid."

This work is among the first studies to directly show that EBV's EBNA1 protein can upregulate cancer-related genes in HPV-positive cervical cancer cells. The findings offer new insight into how EBV may exacerbate disease severity and suggest that co-infection with EBV could make cervical cancer more aggressive. However, the authors emphasize that further research is needed to validate these findings, particularly through in vivo studies and protein-level analysis. Additionally, they aim to investigate the possibility of therapeutic intervention with EBNA1 or its downstream targets.

By revealing a potential molecular interaction between EBV and HPV in cervical cancer, this study highlights the complexity of virus-associated cancers and the need for continued research of viral contributions to cancer biology.