Regulation of autophagy by high‐ and low‐risk human papillomaviruses

Abstract

Summary While high‐risk human papillomavirus (HR‐HPV) infection is related to the development of cervical, vulvar, anal, penile and oropharyngeal cancer, low‐risk human papillomavirus (LR‐HPV) infection is implicated in about 90% of genital warts, which rarely progress to cancer. The carcinogenic role of HR‐HPV is due to the overexpression of HPV E5, E6 and E7 oncoproteins which target and modify cellular proteins implicated in cell proliferation, apoptosis and immortalization. LR‐HPV proteins also target and modify some of these processes; however, their oncogenic potential is lower than that of HR‐HPV. HR‐HPVs have substantial differences with LR‐HPVs such as viral integration into the cell genome, induction of p53 and retinoblastoma protein degradation, alternative splicing in HR‐HPV E6‐E7 open reading frames, among others. In addition, LR‐HPV can activate the autophagy process in infected cells while HR‐HPV infection deactivates it. However, in cancer HR‐HPV might reactivate autophagy in advance stages. Autophagy is a catabolic process that maintains cell homoeostasis by lysosomal degradation and recycling of damaged macromolecules and organelles; nevertheless, depending upon cellular context autophagy may also induce cell death. Therefore, autophagy can contribute either as a promotor or as a suppressor of tumours. In this review, we focus on the role of HR‐HPV and LR‐HPV in autophagy during viral infection and cancer development. Additionally, we review key regulatory molecules such as microRNAs in HPV present during autophagy, and we emphasize the potential use of cancer treatments associated with autophagy in HPV‐related cancers.

It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer

“…Specifically, approximately 70% of these cancers are caused by HPV16 and HPV18 genotypes [10,11,39,40]; these strains are detected significantly more often in biopsies of malignant tonsillar disease than in benign tonsillar pathology [41,42]. [43]-which modulates EGFR signaling [44], downregulates CD1d [45], prevents MHCI trafficking [46], and regulates autophagy [47]. Epithelial cells undergo proliferation and transformation prior to the lytic phase of the virus's life cycle, primarily mediated by E6 (which degrades p53) and E7 (which similarly degrades Rb) [48].…”

“…Microabrasions in tonsillar epithelium lead to HPV infection of basilar and epithelial cells. Basilar cells undergo lateral expansion during the non-lytic phase of the viral cycle, primarily mediated by E5[43]-which modulates EGFR signaling[44], downregulates CD1d[45], prevents MHCI trafficking[46], and regulates autophagy[47]. Epithelial cells undergo proliferation and transformation prior to the lytic phase of the virus's life cycle, primarily mediated by E6 (which degrades p53) and E7 (which similarly degrades Rb)[48].…”

Human Papillomavirus Type 16 Early Protein E7 Activates Autophagy through Inhibition of Dual-Specificity Phosphatase 5

“…For instance, previous studies showed that classical swine fever virus [ 15 ] and bovine ephemeral fever virus [ 16 ] induce autophagy during viral replication, while inhibition of virus-induced autophagy with aspirin suppressed viral replication. Similarly, HPV also exploits the autophagic machinery for infection and proliferation of infected epithelial cells, although the role of autophagy appears to be less clear-cut as it can act as both tumor suppressor and a promoter [ 17 ]. Furthermore, the relationship between HPV16 E7 and autophagy also seems contradictory.…”

Redox‐sensitive signalling pathways regulated by human papillomavirus in HPV‐related cancers

“…HR-HPV induces cancer through its proteins such as E6 and E7 oncoproteins, which are associated with different molecules such as p53 and pRb and organelles such as mitochondria. 1 Also, HPV proteins regulate different processes such as autophagy 2 and apoptosis, 3 among others.…”