Regulation of Wnt/β-catenin signaling by herpesviruses

Abstract

The Wnt/β-catenin signaling pathway is instrumental in successful differentiation and proliferation of mammalian cells. It is therefore not surprising that the herpesvirus family has developed mechanisms to interact with and manipulate this pathway. Successful coexistence with the host requires that herpesviruses establish a lifelong infection that includes periods of latency and reactivation or persistence. Many herpesviruses establish latency in progenitor cells and viral reactivation is linked to host-cell proliferation and differentiation status. Importantly, Wnt/β-catenin is tightly connected to stem/progenitor cell maintenance and differentiation. Numerous studies have linked Wnt/β-catenin signaling to a variety of cancers, emphasizing the importance of Wnt/β-catenin pathways in development, tissue homeostasis and disease. This review details how the alpha-, beta-, and gammaherpesviruses interact and manipulate the Wnt/β-catenin pathway to promote a virus-centric agenda.

Disruption of innate defense responses by endoglycosidase HPSE promotes cell survival

“…Numerous protein interactions and regulators of β-catenin have been characterized, with one known transcriptional co-activator being CBP for DNA binding. The association between this prosurvival factor and infection remains understudied as only a small number of studies exist linking HSV-1 or other viral infection to β-catenin activation (42)(43)(44). In this study, we show that multiple commercially available compounds targeting CREB and β-catenin systems demonstrate antiviral efficacy against HSV-1.…”

Curcumin reversed chronic tobacco smoke exposure induced urocystic EMT and acquisition of cancer stem cells properties via Wnt/β-catenin

“… 18 Numerous studies have suggested the important functions of Wnt/ β -catenin signaling in several cancers. 19 In the absence of Wnt stimulation, β -catenin is phosphorylated by a destruction complex consisting of GSK3 β , CK1, Axin1, Axin2 and APC, resulting in the β -catenin degradation. Upon binding of Wnt, phosphorylation of β -catenin is blocked and allows β -catenin to dissociate from the destruction complex.…”

“…Then, β -catenin accumulates in cytoplasm that results in translocation of β -catenin to the nucleus and interacts with TCF/LEF to transactivate the downstream target genes including Cyclin D1, c-Myc, CD44 and ALDH etc . 19 , 20 Wnt/ β -catenin signaling pathway is an important inducer of EMT and critical for the maintenance of CSCs. Upon activation by specific ligands, β -catenin is released from the membrane and promotes transcription of genes involved in mesenchymal phenotype induction and the maintenance of CSCs.…”

Molecular Determinants and the Regulation of Human Cytomegalovirus Latency and Reactivation

“…In going forward, WNT is an important signaling pathway to consider in CMV latency as it is critical to the control of latency in other herpesviruses. Herpesviruses typically inhibit WNT signaling during replication and promote WNT signaling for the establishment of latency (Reviewed in [ 141 ]). Both EBV and KHSV target Glycogen synthase kinase 3 α/β (GSK-3) of the WNT destruction complex to prevent the degradation of β-catenin during latency [ 142 , 143 , 144 ].…”