11 Mechanisms of dengue virus-induced bone marrow suppression

Vincent F. La Russa, Bruce L. Innis

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Abstract

Infection with many flaviviruses is associated with transient suppression of haematopoiesis. Of the flaviviruses of man, none are more accessible to clinical and laboratory study than dengue. Consequently, the clinical syndrome of dengue-associated bone marrow suppression has been well documented. A review of experimental dengue infections of volunteers and histopathological studies of bone marrow from patients with severe dengue virus infection suggests that marrow suppression evolves rapidly through several phases: (1) onset of marrow suppression within 3-4 days of infection; (2) onset of host inflammatory responses in the marrow and of fever shortly thereafter; (3) occurrence of a neutrophil nadir on the fourth to fifth day after onset of fever; (4) almost simultaneously, immune activation sufficient to neutralize viraemia and accelerate elimination of infected cells; (5) remission of symptoms; and (6) resolution of cytopenias. Clinical observations and experimental data bear on possible mechanisms of dengue virus-mediated marrow suppression. Work from the authors' laboratory in which long-term bone marrow cultures were used to investigate interactions between dengue virus and bone marrow cells (stromal elements and haematopoietic progenitors) is also reviewed. Long-term marrow culture (LTMC) was a useful experimental system. In vitro, early blast cells as well as the more differentiated haematopoietic elements were abortively infected, killed and eliminated by phagocytosis by specialized marrow macrophages called dendritic cells. Moreover, the ARC from stroma rather than haematopoietic precursors were productively infected. When ARC were infected, stroma failed to support haematopoiesis. Cytokine production by virus-infected stromal cells was altered. A hypothesis is proposed to account for dengue virus-induced marrow suppression. Down-regulation of haematopoiesis is probably a protective mechanism of the microenvironment that limits injury to the marrow stem/progenitor cell compartment during the subsequent process of elimination of infected cells.

Original languageEnglish
Pages (from-to)249-270
Number of pages22
JournalBailliere's Clinical Haematology
Volume8
Issue number1
DOIs
StatePublished - Jan 1 1995

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Dengue Virus
Bone Marrow
Dengue
Hematopoiesis
AIDS-Related Complex
Flavivirus
Fever
Stem Cells
Infection
Severe Dengue
Viremia
Virus Diseases
Stromal Cells
Mesenchymal Stromal Cells
Phagocytosis
Dendritic Cells
Volunteers
Neutrophils
Down-Regulation
Macrophages

ASJC Scopus subject areas

  • Hematology

Cite this

11 Mechanisms of dengue virus-induced bone marrow suppression. / La Russa, Vincent F.; Innis, Bruce L.

In: Bailliere's Clinical Haematology, Vol. 8, No. 1, 01.01.1995, p. 249-270.

Research output: Contribution to journalArticle

La Russa, Vincent F. ; Innis, Bruce L. / 11 Mechanisms of dengue virus-induced bone marrow suppression. In: Bailliere's Clinical Haematology. 1995 ; Vol. 8, No. 1. pp. 249-270.
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