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The effect of small molecules on human papillomavirus (HPV) type 16 late gene expression

Yu, Haoran (2014) MOBN18 20132
Degree Projects in Molecular Biology
Popular Abstract
Antivirals for HPV infection

Human papillomaviruses (HPV) are present in more than 99% of all cervical cancers and HPV-16 is one of the predominant types of HPV infections and account almost for 50% of cervical cancer cases. Although two vaccines are available on the market and showed notable promising in HPV prevention, there are still no available antiviral drugs for HPV infections. In this study, I aimed to find substances that can activate HPV-16 late gene expression and produce highly immunogenic proteins L1 and L2, which in turn can activate host immune response and eliminate the virus.

Promising candidate
A serious of different small molecules were screened for HPV-16 late gene induction including adenosine analogues, DNA... (More)
Antivirals for HPV infection

Human papillomaviruses (HPV) are present in more than 99% of all cervical cancers and HPV-16 is one of the predominant types of HPV infections and account almost for 50% of cervical cancer cases. Although two vaccines are available on the market and showed notable promising in HPV prevention, there are still no available antiviral drugs for HPV infections. In this study, I aimed to find substances that can activate HPV-16 late gene expression and produce highly immunogenic proteins L1 and L2, which in turn can activate host immune response and eliminate the virus.

Promising candidate
A serious of different small molecules were screened for HPV-16 late gene induction including adenosine analogues, DNA methyltransferase inhibitors and histone demethylase inhibitors.

Among all these compounds, the adenosine analogues cordycepin and an unknown substance showed a positive induction on HPV-16 late gene expression. The secreted luciferase assay was used to measure the luciferase level, while the quantative PCR was also applied to investigate which and at what level of it was produced. Based on the results, we speculate that cordycepin mainly inhibited the early polyadenylation site, resulted in read-through into late region and activate the late gene expression. While the unknown substance targeted the gene splice pattern by inhibiting splice accepter SA3358, redirecting the splicing to an exclusive late splice acceptor SA5639 and induce HPV-16 late gene expression. However, the unknown substance could induce a morphology change in HPV-18 infected primary cells, but it did not induce any late gene expression neither in HPV-16 nor 18 infected primary cells.

Advisor: Stefan Schwartz
Master´s Degree Project 45 credits in Molecular biology with specialization in Microbiology. 2014
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Yu, Haoran
supervisor
organization
course
MOBN18 20132
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
4695393
date added to LUP
2014-10-07 11:17:32
date last changed
2014-10-07 11:19:16
@misc{4695393,
  author       = {{Yu, Haoran}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The effect of small molecules on human papillomavirus (HPV) type 16 late gene expression}},
  year         = {{2014}},
}