Detektion und Analyse neuer HPV31-Transkripte

Viac o knihe

In papillomavirus-infected tissue, a biphasic life cycle of the virus occurs. In the undifferentiated cells of the epidermis's lower layers, a constant low copy number of viral genomes is maintained through poorly understood control mechanisms. The productive phase begins in the differentiating cells of the upper layers, where viral DNA is amplified, and infectious particles are formed after the expression of structural proteins. Papillomaviruses possess a small genome with only nine reading frames, which they expand through alternative splicing. A spliced fusion protein, E8È2C, has been characterized as a potent transcriptional repressor. This study identified novel transcripts with splice donors in the E1 reading frame from RNA isolates of HPV 16, -18, and -31 positive cells. These transcripts were confirmed as polyadenylated mRNAs for HPV31. Inactivation of the splice donor SD1534 resulted in a phenotype during the early non-productive phase. While the mutation of SD1534 had a minor impact on initial viral DNA replication, long-term culture of virus-containing cells revealed a drastic reduction in viral copy number. Thus, SD1534 is essential for the replication of HPV31 genomes in long-term cultures, suggesting a regulatory role of splice signals within the E1 gene for papillomavirus replication.