Cytomegalovirus infection and pathogenesis in the human placenta

Abstract

Human cytomegalovirus (HCMV) is the most common cause of congenital viral infection. Affected children can have permanent neurological complications, including hearing loss, visual impairment and mental retardation(1-3). In Australia, 57% of women are seronegative and at risk for primary infection and transmission of virus to the fetus during pregnancy(4). Despite its public health significance, the specific molecular and cellular basis of HCMV replication in the human placenta and pathogenesis associated with poor clinical outcome are unknown. Direct fetal infection is involved in severe cases of neuropathology and infection of the placenta can impair its development and functions resulting in a hypoxic environment(5-8) and stillbirth(6,9,10). Gestational age at the time of infection is an important determinant of outcome. The rates of virus transmission increase from 30% in first trimester to over 70% in third trimester suggesting different mechanisms for overcoming the placental barrier(2). Remarkable insights into viral pathogenesis factors that function in the tissue environment have been gained by studying congenitally infected placentas and explants infected by clinical strains ex vivo. Together these studies revealed that direct infection of specialised placental cells and paracrine factors contribute to impaired development and functional defects.