Selective modulation of Wnt-binding receptor tyrosine kinase ROR2 expression by human cytomegalovirus regulates trophoblast migration.

Cytomegalovirus (CMV) infection during pregnancy may lead to adverse pregnancy outcomes and permanent neurological disabilities in infants infected in utero. Congenital CMV disease of the foetus and neonate results from both direct viral cytopathic damage and indirect effects through placental dysfunction. Infection specifically alters Wnt signalling, an essential pathway involved in trophoblast migration and placental development. We examined CMV regulation of trophoblast migration. This virus controls expression of Wnt-binding receptor tyrosine kinase ROR2, but not alternate receptor tyrosine kinases ROR1 or RYK. Ectopic expression of ROR2 reduced Wnt5a-induced trophoblast migration, whilst overexpression of ROR1 or RYK did not affect trophoblast migration. CMV infection increased ROR2 protein expression in trophoblasts, with no effect on ROR1 and RYK expression. These data further support the proposal that specific inhibition of this mechanism may be a target for therapeutic intervention to reduce placental damage and consequent foetal disease due to congenital CMV infection.