Dengue viruses infect human megakaryocytes, with probable clinical consequences.

Abstract:

: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.

journal_name

PLoS Negl Trop Dis

authors

Vogt MB,Lahon A,Arya RP,Spencer Clinton JL,Rico-Hesse R

doi

10.1371/journal.pntd.0007837

subject

Has Abstract

pub_date

2019-11-25 00:00:00

pages

e0007837

issue

11

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-19-00780

journal_volume

13

pub_type

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