Elsevier

Microbial Pathogenesis

Volume 139, February 2020, 103923
Microbial Pathogenesis

Impact of HPV E5 on viral life cycle via EGFR signaling

https://doi.org/10.1016/j.micpath.2019.103923Get rights and content

Highlights

  • HPV E5 causes upregulation of EGFR signaling pathway.

  • HPV E5 contributes to the completion of the viral life-cycle by generating the adequate cellular environment.

  • E5 delays differentiation and allows hyperproliferation of keratinocytes.

Abstract

Oncoprotein E5 is gaining popularity with time as the third transforming protein of Human Papillomavirus (HPV). Extensive proliferation is the distinguished feature of developing cancers, and E5 is able to stimulate keratinocytes proliferation via upregulation of EGFR signaling pathway. Thus E5 is thought to indirectly contribute to the completion of the viral life-cycle by generating the adequate cellular environment. By amplifying EGFR signaling E5 delays differentiation and allows hyperproliferation of keratinocytes which otherwise would have followed a normal differentiation pathway. Thus exploring the mechanisms by which HPV E5 regulates signaling by EGFR receptors in detail suggest new ways of inhibiting HPV-mediated disease progression.

Section snippets

Introduction to HPV E5

During its lifetime, a virus evolves in many ways to overcome the obstacles that stand in the way of a persistent infection. Human Papillomavirus (HPV), like any other virus has evolved successfully to overcome many "obstacles" that the host body provides. Papillomavirus life cycle is inseparably linked to the differentiation program of the host cell, the keratinocyte [1]. The ability of HPV to replicate its genome in replication incompetent differentiating keratinocytes is a major triumph of

Oncogenic potential of E5

Previously E5 was considered to exert its effects mainly through interactions with host proteins. In actual fact, 16E5 expression in vitro has been observed to condition the expression of 25–179 cellular genes depending on the type of cell and conditions of the experiment [26,27]. Over the last few decades, various studies reported E5's ability to temper variety of cellular pathways. Principally, E5 involvement has been seen in the activation and enhancement of the epidermal growth factor

Summary

Human papillomavirus infect stratified squamous epithelium and their life cycle is inseparably connected to the differentiation program of keratinocytes. Thus for the virus to thrive in such an environment it has evolved in various ways and stimulating positive regulation of EGFR signaling by E5 is one of the many ways. Elucidating the mechanisms employed by viral E5 to thwart negative regulation of growth factor signaling may point out new strategies to prevent progression of HPV induced

Declaration of competing interest

No conflict of interest is declared by the authors.

Acknowledgements

We are obliged to the Higher Education Commission of Pakistan and the recurring budget of ASAB provided by NUST for providing us the opportunity to conduct this review.

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    1

    Present address: Abasyn University, Peshawar.

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