The Wnt pathway: a key network in cell signalling dysregulated by viruses

Abstract

Viruses are obligate parasites dependent on host cells for survival. Viral infection of a cell activates a panel of pattern recognition receptors that mediate antiviral host responses to inhibit viral replication and dissemination. Viruses have evolved mechanisms to evade and subvert this antiviral host response, including encoding proteins that hijack, mimic and/or manipulate cellular processes such as the cell cycle, DNA damage repair, cellular metabolism and the host immune response. Currently, there is an increasing interest whether viral modulation of these cellular processes, including the cell cycle, contributes to cancer development. One cellular pathway related to cell cycle signalling is the Wnt pathway. This review focuses on the modulation of this pathway by human viruses, known to cause (or associated with) cancer development. The main mechanisms where viruses interact with the Wnt pathway appear to be through (i) epigenetic modification of Wnt genes; (ii) cellular or viral miRNAs targeting Wnt genes; (iii) altering specific Wnt pathway members, often leading to (iv) nuclear translocation of β-catenin and activation of Wnt signalling. Given that diverse viruses affect this signalling pathway, modulating Wnt signalling could be a generalised critical process for the initiation or maintenance of viral pathogenesis, with resultant dysregulation contributing to virus-induced cancers. Further study of this virus-host interaction may identify options for targeted therapy against Wnt signalling molecules as a means to reduce virus-induced pathogenesis and the downstream consequences of infection. Copyright © 2016 John Wiley & Sons, Ltd.

Exploration of Survival Traits, Probiotic Determinants, Host Interactions, and Functional Evolution of Bifidobacterial Genomes Using Comparative Genomics

“…These signaling processes are pivotal for the multi-cellular organisms, as cells need to communicate extensively among each other and with the environment in order to coordinate actions for proper functioning and the well-being of the organism against the viral infection. The predicted interacting signaling pathways in the humans primarily include Ras, MAPK, PI3K-Akt, cAMP, Rap1, ErbB, Jak-STAT, Sphingolipid, TNF, FoxO, and Wnt, which have been demonstrated to play significant roles in the viral pathogenesis in several studies [ 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 ]. The highest interactions of bifidobacterial proteins with these signaling processes of “Infectious Diseases: Viral” pathways suggest a significant bifidobacterial role in the pathogenies and prognosis of the viral infections.…”

Viruses as key modulators of the TGF‐β pathway; a double‐edged sword involved in cancer

“…39,40 HBV chronic infection is currently estimated to influence almost 240 million people, globally, of which approximately 10% have an increased risk of developing cirrhosis and HCC. 4,41 Similar to HCV, HBV also interacts with the TGF-β pathway, a phenomenon mainly mediated by HBV X protein (HBx), which may exert diverse effects on the pathogenesis of the HBV-mediated liver pathologies 7,21,42,43 (Figure 3). Evidence by Murata further supported the hypothesis that the TGF-β pathway is directly involved in liver tumorigenesis, where HBx was shown to switch the target of hepatocytic TGF-β signaling from the TGFbRI/ pSmad3C/p21 anti-tumor pathway to the JNK/pSmad3L/c-Myc tumor supportive pathway in the early stages of liver carcinogenesis.…”

The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

“…The activation of Wnt signaling has been demonstrated for the human polyoma virus JC (134), Epstein–Barr virus (135), and Kaposi’s sarcoma-associated herpesvirus (136), being just a few examples of viruses which are known to lead to tumor development, an issue very recently reviewed (137). With regard to viral infections of the airways, adenoviruses are known to strongly interfere with the Wnt signaling machinery as several factors are heavily regulated during infection (138).…”