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Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
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Retinoblastoma Protein Is Required for Epstein-Barr Virus Replication in Differentiated Epithelia
Julia E Myers1,2,3,4, Danielle L Schaal1,2,3,4, Ebubechukwu H Nkadi1,3,4
1Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, USA.
Journal of Virology
|January 31, 2023
Summary
Retinoblastoma (Rb) protein is crucial for Epstein-Barr virus (EBV) replication in differentiated epithelial cells and Burkitt lymphoma. Loss of Rb impairs EBV early gene expression and viral replication, offering insights into HPV-EBV coinfections.
Area of Science:
- Virology
- Cell Biology
- Oncology
Background:
- Coinfection with human papillomavirus (HPV) and Epstein-Barr virus (EBV) is observed in oropharyngeal squamous cell carcinoma.
- HPV oncoprotein E7 degrades retinoblastoma (Rb) family proteins, impacting EBV replication.
- The role of the cell cycle in differentiated tissues for EBV replication is not fully understood.
Purpose of the Study:
- To investigate the role of pRb in EBV lytic replication in differentiated epithelia and EBV-positive Burkitt lymphoma (BL).
- To elucidate the mechanism by which HPV E7 inhibits EBV replication through pRb degradation.
Main Methods:
- Organotypic epithelial raft cultures were used to model differentiated epithelia.
- Genetic interference (knockdown) was employed to study the function of pRb.
- EBV-positive Burkitt lymphoma cells (Akata BX1) were used to study EBV reactivation.
Main Results:
- pRb knockdown in differentiated epithelia reduced EBV lytic replication and blocked early gene expression (EA-D).
- pRb loss in epithelia increased S-phase markers and altered p107/p130 levels.
- In contrast, pRb knockdown in BL cells reduced EBV reactivation, decreased PRDM1/Blimp1, and increased c-Myc.
Conclusions:
- pRb is essential for efficient EBV lytic replication in both differentiated epithelia and BL cells.
- HPV E7's inhibition of EBV replication is mediated through pRb degradation, impacting cell cycle progression and viral gene expression.
- pRb suppresses c-Myc, which is required for efficient EBV replication in BL cells, providing a mechanism for HPV-mediated interference with EBV replication.
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