Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome

Abstract

BackgroundAn estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants.MethodsCells and organs involved in RV replication were identified in paraffin-embedded autopsy tissues from three fatal case-patients by histopathologic examination and immunohistochemical (IHC) staining using a rabbit polyclonal RV antibody. Normal rabbit antisera and RV antisera preabsorbed with highly purified RV served as negative controls.ResultsRV antigen was found in interstitial fibroblasts in the heart, adventitial fibroblasts of large blood vessels, alveolar macrophages, progenitor cells of the outer granular layer of the brain, and in capillary endothelium and basal plate in the placenta. The antibody specificity was verified by IHC staining of multiple tissue sections from other infectious disease cases. RV infection of each cell type is consistent with abnormalities which have been identified in patients with CRS, in the heart, large blood vessels, and brain. Antigen distribution was consistent with inflammatory response to vascular injury and systemic spread of RV.ConclusionsThe identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS.

Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

“…We also noticed that in all microcephaly cases that were positive by tissue RT-PCR, maternal symptom onset occurred during the first trimester, which might suggest that the virus can cause abnormal brain development when infection occurs early in organogenesis. Previous studies of rubella reported that the risk for fetal infection with congenital anomalies is highest when exposure/infection occurred before 11–12 weeks of gestation and sharply decreased with increasing gestational age ( 32 ) . …”

Pathology of congenital Zika syndrome in Brazil: a case series

“…In addition to genetic, toxic, iatrogenic, and other noninfectious causes, congenital malformations can be caused by the vertical transmission of viruses, bacteria, and parasites such as cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Treponema pallidum. [15][16][17][18][19] Infection during the fi rst trimester of pregnancy is of particular concern with most of these agents and can be associated with serious consequences. On the other hand, cytomegalovirus infection at any point during pregnancy can result in severe CNS sequelae.…”

Clinically confirmed congenital rubella syndrome: the role of echocardiography

“…Rubella virus antigens were detected in myocardial fibroblasts of two patients, although they did not have histological signs of myocarditis or viral antigens in their cardiac myocytes (10). Additional evidence of the presence of viral antigens in adventitial fibroblasts of large blood vessels helps explain the possible mechanisms for congenital cardiovascular malformations (patent ductus arteriosus and branch pulmonary artery stenosis) in CRS patients.…”