Human Papillomavirus Type 16 E6 induces cell competition

Author:

Brimer Nicole,Pol Scott VandeORCID

Abstract

AbstractHigh risk human papillomavirus (HPV) infections induce squamous epithelial tumors in which the virus replicates. Initially, the virus-infected epithelial cells are untransformed, but expand in both number and area at the expense of normal squamous epithelial cells. How this occurs is unknown, but is presumed to be due to viral oncogene expression. We have developed an in vitro assay in which colonies of post-confluent HPV16 expressing cells outcompete confluent surrounding normal keratinocytes for surface area. The enhanced cell competition induced by the complete HPV16 genome is conferred by E6 expression alone, and not by individual expression of E5 or E7. In traditional oncogene assays, E7 is a more potent oncogene than E6, but such assays do not include interaction with normal surrounding cells. These new results separate classic oncogenicity that is primarily conferred by E7, from cell competition that we show is primarily conferred by E6, and provides a new biological role for E6 oncoproteins from high risk human papillomaviruses.ImportanceHigh risk papillomavirus infections induce epithelial tumors, some of which evolve into malignancies. The development and maintenance of cancer is due to the virally encoded E6 and E7 oncoproteins. How a virally infected keratinocyte out-competes normal uninfected keratinocytes has been unknown. The present work shows that the enhanced competition of HPV16-infected cells is primarily due to the expression of the E6 oncoprotein and not the E7 or E5 oncoproteins. This work shows the importance of measuring oncoprotein traits in the context of cell competition with uninfected cells, and shows the potential of papillomavirus oncoproteins to be novel genetic probes for the analysis of cell competition.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3