Abstract
Cardiovascular abnormalities are the leading cause of neonatal death among patients with congenital rubella syndrome (CRS). Although persistence of rubella virus (RV) in fetal endothelium has been repeatedly suggested as a possible cause of cardiovascular birth defects, evidence of the permissiveness of fetal endothelial cells to RV is lacking. In this study we evaluated the ability of RV to infect and persist in primary fetal endothelial cells derived from human umbilical vein (HUVEC). We found that wild type (wt) low passage clinical RV productively infected HUVEC cultures without producing cytopathology or ultrastructural changes. RV did not inhibit host cell protein synthesis, cell proliferation, or interfere with the cell cycle. Persistently infected cultures were easily established at low and high multiplicities of infection (MOI) with both laboratory and wt clinical RV strains. However, synchronous infections of entire HUVEC monolayers were only observed with clinical RV strains. The release of infectious virions into media remained at consistently high levels for several subcultures of infected HUVEC. The results indicate that macrovascular fetal endothelial cells are highly permissive to RV and allow slow persistent RV replication. The findings provide more evidence for the suggestion that vascular pathologies in CRS are triggered by persistent rubella virus infection of the endothelium.
Highlights
Rubella virus (RV) is a single stranded RNA virus of positive polarity belonging to the genus Rubivirus, in the family Togaviridae
Since pathologic lesions are often observed in large elastic blood vessels of congenital rubella syndrome (CRS) patients including umbilical vein [14], we used primary cultures of endothelial cells derived from umbilical vein to examine the susceptibility of fetal endothelial cells to RV
In this study we investigated RV persistence in primary fetal endothelial cells since this cell type is involved in pathogenesis in congenitally infected fetuses and abnormal endothelium is found in CRS cases
Summary
Rubella virus (RV) is a single stranded RNA virus of positive polarity belonging to the genus Rubivirus, in the family Togaviridae. Postnatal rubella infection causes mild febrile illness accompanied by maculopapular rash and lymphadenopathy, while maternal infections during the first trimester of pregnancy often result in a combination of birth defects in newborns called congenital rubella syndrome (CRS) [1]. National immunization programs have led to the elimination or decline in incidence of postnatal rubella and CRS in many developed countries, approximately 100,000 CRS cases per year still occur worldwide [2]. Vascular abnormalities can lead to a number of clinical manifestations with patent ductus arteriosus, pulmonary artery stenosis and septal and valve defects in heart being the most frequent [11,12]. Other clinical manifestations of congenital rubella, such as general growth retardation, deafness and neurodegenerative damage, may be due to vascular insufficiency leading to nutrient deprivation rather than a result of direct viral damage [4]
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