Regulation of Autophagy in Cells Infected With Oncogenic Human Viruses and Its Impact on Cancer Development.

Benedetta Pagni,Gian Maria Fimia,Tiziana Vescovo,Manuela Antonioli,Mauro Piacentini

doi:10.3389/fcell.2020.00047

Abstract

About 20% of total cancer cases are associated to infections. To date, seven human viruses have been directly linked to cancer development: high-risk human papillomaviruses (hrHPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein–Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus 1 (HTLV-1). These viruses impact on several molecular mechanisms in the host cells, often resulting in chronic inflammation, uncontrolled proliferation, and cell death inhibition, and mechanisms, which favor viral life cycle but may indirectly promote tumorigenesis. Recently, the ability of oncogenic viruses to alter autophagy, a catabolic process activated during the innate immune response to infections, is emerging as a key event for the onset of human cancers. Here, we summarize the current understanding of the molecular mechanisms by which human oncogenic viruses regulate autophagy and how this negative regulation impacts on cancer development. Finally, we highlight novel autophagy-related candidates for the treatment of virus-related cancers.

Highlights

High-risk human papillomaviruses and Merkel cell polyomavirus (MCPyV) are implicated in the development of mucosal and cutaneous cancers
The incidence of viral-associated cancers is substantially lower than virus prevalence, and tumors occur in the context of persistent infections where the immune system is perturbed (Mesri et al, 2014)
The known seven oncogenic viruses have been all described to impact on autophagy, with different outcomes depending on cellular tropism and infection stage (Silva and Jung, 2013)

Summary

Introduction

High-risk human papillomaviruses (hrHPV) and Merkel cell polyomavirus (MCPyV) are implicated in the development of mucosal and cutaneous cancers. It is well established that, in order to favor their replication, HBV and HCV can positively regulate the autophagy process, both directly, through the influence of viral elements on autophagic proteins, and indirectly, through the activation of cellular stress responses, which, in turn, stimulate autophagy.

Results

Conclusion