Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome
Background: An 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 posi...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396415302334 |
| _version_ | 1811288891724922880 |
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| author | Mihaela Lazar Ludmila Perelygina Roosecelis Martines Patricia Greer Christopher D. Paddock Gheorghe Peltecu Emilia Lupulescu Joseph Icenogle Sherif R. Zaki |
| author_facet | Mihaela Lazar Ludmila Perelygina Roosecelis Martines Patricia Greer Christopher D. Paddock Gheorghe Peltecu Emilia Lupulescu Joseph Icenogle Sherif R. Zaki |
| author_sort | Mihaela Lazar |
| collection | DOAJ |
| description | Background: An 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.
Methods: Cells 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.
Results: RV 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.
Conclusions: The identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS. |
| first_indexed | 2024-04-13T03:45:25Z |
| format | Article |
| id | doaj.art-187f709423d5496394f1694749123f9d |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-13T03:45:25Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-187f709423d5496394f1694749123f9d2022-12-22T03:04:02ZengElsevierEBioMedicine2352-39642016-01-013C869210.1016/j.ebiom.2015.11.050Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella SyndromeMihaela Lazar0Ludmila Perelygina1Roosecelis Martines2Patricia Greer3Christopher D. Paddock4Gheorghe Peltecu5Emilia Lupulescu6Joseph Icenogle7Sherif R. Zaki8Measles, Mumps, Rubella and Herpesvirus Laboratory Branch, Division of Viral Diseases, 1600 Clifton Rd, Atlanta, GA, USAMeasles, Mumps, Rubella and Herpesvirus Laboratory Branch, Division of Viral Diseases, 1600 Clifton Rd, Atlanta, GA, USAInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USAInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USAInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USAFilantropia Clinical Hospital, 11-13 Blvd. Ion Mihalache, Bucharest, RomaniaNational Laboratory for Measles and Rubella, National Institute of Research-Development for Microbiology and Immunology “Cantacuzino”, 103 Splaiul Independenței, Bucharest, RomaniaMeasles, Mumps, Rubella and Herpesvirus Laboratory Branch, Division of Viral Diseases, 1600 Clifton Rd, Atlanta, GA, USAInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USABackground: An 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. Methods: Cells 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. Results: RV 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. Conclusions: The identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS.http://www.sciencedirect.com/science/article/pii/S2352396415302334Congenital rubella syndrome (CRS)CRS pathologyImmunohistochemistryFatal casesAutopsy |
| spellingShingle | Mihaela Lazar Ludmila Perelygina Roosecelis Martines Patricia Greer Christopher D. Paddock Gheorghe Peltecu Emilia Lupulescu Joseph Icenogle Sherif R. Zaki Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome EBioMedicine Congenital rubella syndrome (CRS) CRS pathology Immunohistochemistry Fatal cases Autopsy |
| title | Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome |
| title_full | Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome |
| title_fullStr | Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome |
| title_full_unstemmed | Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome |
| title_short | Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome |
| title_sort | immunolocalization and distribution of rubella antigen in fatal congenital rubella syndrome |
| topic | Congenital rubella syndrome (CRS) CRS pathology Immunohistochemistry Fatal cases Autopsy |
| url | http://www.sciencedirect.com/science/article/pii/S2352396415302334 |
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