Modulation of Wnt Signaling Pathway during Cytomegalovirus Latency and Reactivation

The Wnt signaling pathway is one of the key pathways involved in hematopoietic progenitor cell (HPC) proliferation and differentiation. Human cytomegalovirus (HCMV) establishes latency in CD34⁺ HPCs and reactivation of the virus is intimately linked with cellular differentiation. In this review, we describe the unique strategies HCMV uses to control the Wnt signaling pathway during latency and reactivation.

In solid organ transplant recipients, low plasma levels of the Wnt antagonist DKK1 is a predictor of treatment failure and HCMV reactivation. HCMV encodes viral gene products, including UL8, US28 and miRNAs, able to modulate the Wnt signaling pathway that are important for viral reactivation .

HCMV promotes activation of the Wnt signaling pathway to mediate efficient reactivation, although the downstream effects of Wnt activation have yet to be examined. Characterizing the HCMV viral gene products that manipulate the Wnt pathway will be instrumental for the development of new antiviral therapies.