The Emerging Role of Hedgehog Signaling in Viral Infections

Abstract

The hedgehog (HH) signaling pathway is one of the key pathways that is indispensable for many developmental processes and postnatal tissue homeostasis. Dysregulated HH signaling could lead to developmental disorders and tumorigenesis in a variety of tissues via inherited or sporadic mutation, gene overexpression, and crosstalk with other signaling pathways. Recently, accumulating evidence has shown that HH signaling is targeted by viruses to facilitate viral transcription, immune evasion, and uncontrolled growth, leading to effective viral replication and pathogenesis. In this study, we will summarize recent advances in functional interaction between HH signaling and different types of viruses, particularly focusing on the pathological role of HH signaling in viral infections and related diseases.

Identification of Proteins and Genes Associated with Hedgehog Signaling Pathway Involved in Neoplasm Formation Using Text-Mining Approach

“…7. The role of the Hh pathway in cancer and developmental disorders is well known [54,[61][62][63][64] , but involvement of the Hh pathway in infectious diseases is less studied [64][65][66] .…”

“…7). Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Epstein-Barr Virus (EBV), Human PapillomaVirus (HPV), Human Immunodeficiency Virus (HIV), Human T-cell Leukemia Virus type I (HTLV-1), Influenza A Virus (IAV), and Kaposi's Sarcoma-associated HerpesVirus (KSHV) are known to induce pathological processes by regulating the expression, protein stability, and subcellular localization of Hh pathway components [64,65] . For instance, the hepatitis B pathway has the highest number of nodes shared with Hh-interacting proteins (Fig.…”

The Role of Hedgehog Signaling Pathway in Head and Neck Squamous Cell Carcinoma

“…However, this mechanism might be disturbed by KSHV infection, which utilizes the host PDGF receptor (PDGFR) and generates tumorigenesis [ 157 ]. Moreover, it is well known that HBV and HCV are involved in the activation of HH signaling in hepatocellular carcinoma (HCC), what contributes to several processes related strictly to HCC tumorigenesis like EMT, maintenance of CSCs, metastasis, and resistance to therapy [ 158 ]. Some authors revealed the aberration of HH signaling by HCV in liver fibrosis and HCC but also proposed the possibility of HH inhibitors as a potential target in future therapy [ 159 , 160 ].…”

“…Some authors revealed the aberration of HH signaling by HCV in liver fibrosis and HCC but also proposed the possibility of HH inhibitors as a potential target in future therapy [ 159 , 160 ]. Researchers are still investigating the relationship between HCV and HH signaling components to establish the role of both factors in the pathogenesis of HCC [ 158 ]. The association between the HH signaling pathway and HPV/E6 protein was confirmed in the murine model of cervical cancer [ 161 ].…”

“…Interestingly, such a correlation between p16 and PTCH1 expression was identified by Leovic et al in OPSCC [ 66 ]. Aberrant activation of HH signaling seems to play a significant role in EBV-induced nasopharyngeal carcinoma [ 158 ]. It was reported that HH signaling in epithelial cells is activated by EBV, which results in the overexpression of stemness genes [ 158 ].…”