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CD46 facilitates entry and dissemination of human cytomegalovirus

Human cytomegalovirus (CMV) causes a wide array of disease to diverse populations of immune-compromised individuals. Thus, a more comprehensive understanding of how CMV enters numerous host cell types is necessary to further delineate the complex nature of CMV pathogenesis and to develop targeted th...

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Autores principales: Stein, Kathryn R., Gardner, Thomas J., Hernandez, Rosmel E., Kraus, Thomas A., Duty, James A., Ubarretxena-Belandia, Iban, Moran, Thomas M., Tortorella, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586906/
https://www.ncbi.nlm.nih.gov/pubmed/31221976
http://dx.doi.org/10.1038/s41467-019-10587-1
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author Stein, Kathryn R.
Gardner, Thomas J.
Hernandez, Rosmel E.
Kraus, Thomas A.
Duty, James A.
Ubarretxena-Belandia, Iban
Moran, Thomas M.
Tortorella, Domenico
author_facet Stein, Kathryn R.
Gardner, Thomas J.
Hernandez, Rosmel E.
Kraus, Thomas A.
Duty, James A.
Ubarretxena-Belandia, Iban
Moran, Thomas M.
Tortorella, Domenico
author_sort Stein, Kathryn R.
collection PubMed
description Human cytomegalovirus (CMV) causes a wide array of disease to diverse populations of immune-compromised individuals. Thus, a more comprehensive understanding of how CMV enters numerous host cell types is necessary to further delineate the complex nature of CMV pathogenesis and to develop targeted therapeutics. To that end, we establish a vaccination strategy utilizing membrane vesicles derived from epithelial cells to generate a library of monoclonal antibodies (mAbs) targeting cell surface proteins in their native conformation. A high-throughput inhibition assay is employed to screen these antibodies for their ability to limit infection, and mAbs targeting CD46 are identified. In addition, a significant reduction of viral proliferation in CD46-KO epithelial cells confirms a role for CD46 function in viral dissemination. Further, we demonstrate a CD46-dependent entry pathway of virus infection in trophoblasts, but not in fibroblasts, highlighting the complexity of CMV entry and identifying CD46 as an entry factor in congenital infection.
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spelling pubmed-65869062019-06-24 CD46 facilitates entry and dissemination of human cytomegalovirus Stein, Kathryn R. Gardner, Thomas J. Hernandez, Rosmel E. Kraus, Thomas A. Duty, James A. Ubarretxena-Belandia, Iban Moran, Thomas M. Tortorella, Domenico Nat Commun Article Human cytomegalovirus (CMV) causes a wide array of disease to diverse populations of immune-compromised individuals. Thus, a more comprehensive understanding of how CMV enters numerous host cell types is necessary to further delineate the complex nature of CMV pathogenesis and to develop targeted therapeutics. To that end, we establish a vaccination strategy utilizing membrane vesicles derived from epithelial cells to generate a library of monoclonal antibodies (mAbs) targeting cell surface proteins in their native conformation. A high-throughput inhibition assay is employed to screen these antibodies for their ability to limit infection, and mAbs targeting CD46 are identified. In addition, a significant reduction of viral proliferation in CD46-KO epithelial cells confirms a role for CD46 function in viral dissemination. Further, we demonstrate a CD46-dependent entry pathway of virus infection in trophoblasts, but not in fibroblasts, highlighting the complexity of CMV entry and identifying CD46 as an entry factor in congenital infection. Nature Publishing Group UK 2019-06-20 /pmc/articles/PMC6586906/ /pubmed/31221976 http://dx.doi.org/10.1038/s41467-019-10587-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Stein, Kathryn R.
Gardner, Thomas J.
Hernandez, Rosmel E.
Kraus, Thomas A.
Duty, James A.
Ubarretxena-Belandia, Iban
Moran, Thomas M.
Tortorella, Domenico
CD46 facilitates entry and dissemination of human cytomegalovirus
title CD46 facilitates entry and dissemination of human cytomegalovirus
title_full CD46 facilitates entry and dissemination of human cytomegalovirus
title_fullStr CD46 facilitates entry and dissemination of human cytomegalovirus
title_full_unstemmed CD46 facilitates entry and dissemination of human cytomegalovirus
title_short CD46 facilitates entry and dissemination of human cytomegalovirus
title_sort cd46 facilitates entry and dissemination of human cytomegalovirus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586906/
https://www.ncbi.nlm.nih.gov/pubmed/31221976
http://dx.doi.org/10.1038/s41467-019-10587-1
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