Chapter 6 : Regulation of Transcription and Replication by Human Papillomaviruses

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This chapter concentrates on the mechanisms by which human papillomaviruses (HPVs) regulate viral transcription and replication during the productive life cycle. The first studies which examined papillomaviruses concentrated on the bovine papillomaviruses (BPVs) with the hope that BPV-1 would serve as a useful model for the high-risk human viruses. While many similarities exist between the two viral types, a significant number of differences are also present. For this reason, the author concentrates the discussion on the HPV types and refers to BPVs only when no information is available in the human system. In order to understand how viral gene expression is regulated during a productive infection, it is first important to describe the transcripts which are synthesized. One of the most remarkable features of HPV transcription is that all early and late transcripts are polycistronic. The E1 and E2 proteins function in viral replication and may also modulate viral expression. A detailed discussion of the role of these proteins in replication is provided in the chapter. In order to further understand the interplay of these two viral functions, the chapter discusses the control of viral replication in detail. Given the tight linkage of late gene expression and amplification to epithelial differentiation, it is likely that cellular factors play important roles.

Citation: Laimins L. 1998. Regulation of Transcription and Replication by Human Papillomaviruses, p 201-223. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch6

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Gene Expression and Regulation
Immune System Proteins
Simian virus 40
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Image of Figure 1
Figure 1

Genomic map of high-risk HPV-31. ORFs designated E indicate ORFs expressed early during infection as well as in basal cells. ORFs designated L indicate late capsid genes. Small black boxes indicate E2 binding sites in the URR. This genomic organization is similar to those of other genital papillomaviruses.

Citation: Laimins L. 1998. Regulation of Transcription and Replication by Human Papillomaviruses, p 201-223. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch6
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Image of Figure 2
Figure 2

Cartoon of differentiating epithelia and a table of viral functions which are induced upon epithelial differentiation. The various epithelial layers are indicated.

Citation: Laimins L. 1998. Regulation of Transcription and Replication by Human Papillomaviruses, p 201-223. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch6
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Image of Figure 3
Figure 3

Transcript map of HPV-31. Transcripts expressed constitutively throughout the epithelia initiate at the early p97 promoter and terminate at the early polyadenylation signal located at the end of the E5 ORF. Late transcripts initiate at the late promoter, p742, and terminate at either the early or the late polyadenylation signals.

Citation: Laimins L. 1998. Regulation of Transcription and Replication by Human Papillomaviruses, p 201-223. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch6
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Image of Figure 4
Figure 4

Origin of replication of HPV-31, indicating the E1 binding site and the two flanking E2 sites. E1 proteins bind to E1 sites as multimeric complexes which can form larger complexes with adjacent E2 dimers.

Citation: Laimins L. 1998. Regulation of Transcription and Replication by Human Papillomaviruses, p 201-223. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch6
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