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Virologica Sinica, 31 (5) : 437, 2016
Letter
HPV18 DNA replication inactivates the early promoter P55 activity and prevents viral E6 expression
1. Tumor Virus RNA Biology Section, RNA Biology Laboratory,
National Cancer Institute, National Institutes of Health, Frederick,
Maryland 21702, USA.
2. Department of Biochemistry and Molecular Genetics, University
of Alabama at Birmingham, Alabama 35294, USA.
3. Department of Microbiology and Immunology, Penn State
University College of Medicine, Hershey, Pennsylvania 17033,
USA.
 Correspondence: zhengt@exchange.nih.gov
(1583.84KB)  
Abstract
HPV18 genome contains two major transcription start sites (TSS) respectively positioned at nt 55 (TSS-55 or promoter P55) and nt 102 (TSS-102 or promoter P102) in the early promoter region upstream of viral E6 open reading frame (ORF). The TATA box driving RNA transcription at the TSS-55 overlaps with a core region of the viral replication origin (Ori), whereas the TATA box for the TSS-102 is downstream and outside of the core Ori. In late stage of HPV18 infection or in highly differentiated keratinocytes, HPV18 DNA replication unwinds the TATA-containing Ori and prevents RNA transcription from the P55 promoter, but not from the P102 promoter. Because RNA transcripts derived from the P55 promoter, but not from the P102 promoter, bears a reasonable length (51 nts) of 5’ untranslational region (5’ UTR), we demonstrated that the P55-derived transcripts are responsible for viral E6 expression and thereby p53 stability. Inhibition of viral DNA replication by phosphonoacetic acid increases the P55 promoter transcription and viral E6 expression, subsequently leading to p53 reduction. Together, our data provide the first evidence that HPV18 DNA replication controls the expression of viral E6 expression from the P55 promoter.
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Received: 8 Oct 2016  Accepted: 8 Oct 2016  Published online: 25 Oct 2016
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