Kolmpäeval 7. märtsil 2018 09:15 toimub TÜ tehnoloogiainstituudis Prof. Dr. rer. nat. Frank Stubenrauch'i külalisseminar teemal “The role of the E8^E2 repressor in the HPV life cycle”

Persistent infections with high-risk human papillomaviruses (HPVs) such as HPV16, -18, and -31 can result in anal, cervical, oropharyngeal, penile, and vaginal cancer. HPV infect undifferentiated keratinocytes, and amplify their DNA genomes to ~100 copies/cell, which requires the viral E1 helicase and the E2 transcription/replication factor. Upon differentiation, infected cells further amplify their genomes to several thousand copies/cell, express the late non-structural E4 protein and the L1 and L2 capsid proteins.

We and others have previously shown that the initial amplification of several HPV in undifferentiated cells is inhibited by the viral E8^E2 protein, which interacts with E2 binding sites on the viral genome. The inhibitory activity is due to the repression of viral transcription which would limit levels of the replication activators E1 and E2 and the direct repression of E1/E2-dependent DNA replication. In long-term replication experiments differences between HPV16 and HPV31 E8^E2 mutant genomes are observed: HPV16 genomes are stably maintained at higher copy numbers whereas HPV31 genomes integrate into the host DNA. Interestingly, HPV16 E8^E2 mutants amplify their genomes to higher levels in differentiated cells than wildtype genomes indicating that E8^E2 also limits productive replication.

Discussion for the following questions:

1) How does E8^E2 repress viral genome replication?

2) Why do HPV encode E8^E2?