Dengue viruses infect human megakaryocytes, with probable clinical consequences.
One of the most important clinical signs of dengue virus infection is the reduction of white blood cells and platelets in human peripheral blood (leukopenia and thrombocytopenia, respectively), which may significantly impair the clearance of dengue virus by the immune system. The cause of thrombocyt...
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ftdoajarticles:oai:doaj.org/article:b582e45b8633485284f50c2802fab1b9 2023-05-15T15:08:31+02:00 Dengue viruses infect human megakaryocytes, with probable clinical consequences. Megan B Vogt Anismrita Lahon Ravi P Arya Jennifer L Spencer Clinton Rebecca Rico-Hesse 2019-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007837 https://doaj.org/article/b582e45b8633485284f50c2802fab1b9 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007837 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007837 https://doaj.org/article/b582e45b8633485284f50c2802fab1b9 PLoS Neglected Tropical Diseases, Vol 13, Iss 11, p e0007837 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007837 2022-12-31T09:21:49Z One of the most important clinical signs of dengue virus infection is the reduction of white blood cells and platelets in human peripheral blood (leukopenia and thrombocytopenia, respectively), which may significantly impair the clearance of dengue virus by the immune system. The cause of thrombocytopenia and leukopenia during dengue infection is still unknown, but may be related to severe suppression of bone marrow populations including hematopoietic stem cells and megakaryocytes, the progenitors of white blood cells and platelets respectively. Here, we explored the possibility that bone marrow suppression, including ablation of megakaryocyte populations, is caused by dengue virus infection of megakaryocytes. We used three different models to measure dengue virus infection and replication: in vitro, in a human megakaryocyte cell line with viral receptors, ex vivo, in primary human megakaryocytes, and in vivo, in humanized mice. All three systems support dengue virus infection and replication, including virus strains from serotypes 1, 2, and 3, and clinical signs, in vivo; all assays showed viral RNA and/or infectious viruses 7-14 days post-infection. Although we saw no significant decrease in cell viability in vitro, there was significant depletion of mature megakaryocytes in vivo. We conclude that megakaryocytes can produce dengue viruses in the bone marrow niche, and a reduction of cell numbers may affect bone marrow homeostasis. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 11 e0007837 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Megan B Vogt Anismrita Lahon Ravi P Arya Jennifer L Spencer Clinton Rebecca Rico-Hesse Dengue viruses infect human megakaryocytes, with probable clinical consequences. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
One of the most important clinical signs of dengue virus infection is the reduction of white blood cells and platelets in human peripheral blood (leukopenia and thrombocytopenia, respectively), which may significantly impair the clearance of dengue virus by the immune system. The cause of thrombocytopenia and leukopenia during dengue infection is still unknown, but may be related to severe suppression of bone marrow populations including hematopoietic stem cells and megakaryocytes, the progenitors of white blood cells and platelets respectively. Here, we explored the possibility that bone marrow suppression, including ablation of megakaryocyte populations, is caused by dengue virus infection of megakaryocytes. We used three different models to measure dengue virus infection and replication: in vitro, in a human megakaryocyte cell line with viral receptors, ex vivo, in primary human megakaryocytes, and in vivo, in humanized mice. All three systems support dengue virus infection and replication, including virus strains from serotypes 1, 2, and 3, and clinical signs, in vivo; all assays showed viral RNA and/or infectious viruses 7-14 days post-infection. Although we saw no significant decrease in cell viability in vitro, there was significant depletion of mature megakaryocytes in vivo. We conclude that megakaryocytes can produce dengue viruses in the bone marrow niche, and a reduction of cell numbers may affect bone marrow homeostasis. |
format |
Article in Journal/Newspaper |
author |
Megan B Vogt Anismrita Lahon Ravi P Arya Jennifer L Spencer Clinton Rebecca Rico-Hesse |
author_facet |
Megan B Vogt Anismrita Lahon Ravi P Arya Jennifer L Spencer Clinton Rebecca Rico-Hesse |
author_sort |
Megan B Vogt |
title |
Dengue viruses infect human megakaryocytes, with probable clinical consequences. |
title_short |
Dengue viruses infect human megakaryocytes, with probable clinical consequences. |
title_full |
Dengue viruses infect human megakaryocytes, with probable clinical consequences. |
title_fullStr |
Dengue viruses infect human megakaryocytes, with probable clinical consequences. |
title_full_unstemmed |
Dengue viruses infect human megakaryocytes, with probable clinical consequences. |
title_sort |
dengue viruses infect human megakaryocytes, with probable clinical consequences. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007837 https://doaj.org/article/b582e45b8633485284f50c2802fab1b9 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 11, p e0007837 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007837 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007837 https://doaj.org/article/b582e45b8633485284f50c2802fab1b9 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007837 |
container_title |
PLOS Neglected Tropical Diseases |
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13 |
container_issue |
11 |
container_start_page |
e0007837 |
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1766339869272965120 |