Regulation of Wnt/β-catenin signaling by herpesviruses

Table 1 Wnt/β-catenin molecular manipulations by human Herpesviridae

Virus	Pathway component	Stabilization, activation or inhibition of pathway component	Outcome	Ref.
Alphaherpesvirinae
HSV-1	β-catenin	Stabilized	β-catenin stabilized, increased transcriptional activity of β-catenin	[35]
	Axin	Stabilized	Reduced host cell apoptosis	[37,38]
	GSK-3	Stabilized	Phosphorylation of APP	[39]
Betaherpesvirinae
HCMV	β-catenin	Inhibited	β-catenin degradation, decrease in β-catenin transcriptional targets	[41]
	Axin	Stabilized	TNKS PARsylation activity inhibited resulting in β-catenin degradation	[50]
	ROR2	Activated	Repression of β-catenin TCF/LEF-1 transcriptional activity	[42]
	GSK-3	Stabilized	Stabilization of pAP and promotion of HCMV replication	[52,53]
Gammaherpesvirinae
EBV	β-catenin	Stabilized	Accumulation of β-catenin in type III latency	[59]
	GSK-3	Inhibited	LMP2A activation of Akt inactivates GSK-3 resulting in β-catenin accumulation	[60,61]
	APC	Activated/inhibited (conflicting results)	LMP1 represses Siah-1 promoting β-catenin accumulation. LMP1 does not promote β-catenin stabilization	[63,64]
KSHV	β-catenin	Stabilized/inhibited (dependent on viral stage?)	Increased transcriptional activity, induction of viral latency/inhibition of LANA mediated transactivation of β-catenin	[66,76,77]
	GSK-3	Inhibited	LANA promotes nuclear accumulation of GSK-3	[67,70]

GSK-3: Glycogen synthase kinase 3; HCMV: Human cytomegalovirus; TNKS: Tankyrase 1 and 2 (PARP5a/b); TCF/LEF-1: T-cell factor/lymphoid enhancer-binding factor 1; pAP: Protein precursor; LMP2A: Latent membrane protein 2A; APC: Adenomatous polyposis coli; LMP1: Latent membrane protein 1; LANA: Latency-associated nuclear antigen; KSHV: Kaposi’s sarcoma-associated herpesvirus.