Dengue virus and the complement alternative pathway

Jillian M. Carr, Sheila Cabezas-Falcon, Joshua G. Dubowsky, Jarrod Hulme-Jones, David L. Gordon

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Dengue disease is an inflammatory-driven pathology, and complement overactivation is linked to disease severity and vascular leakage. Additionally, dysregulation of complement alternative pathway (AP) components has been described, such as upregulation of complement factor D and downregulation of complement factor H (FH), which activate and inhibit the AP, respectively. Thus, the pathology of severe dengue could in part result from AP dysfunction, even though complement and AP activation usually provide protection against viral infections. In dengue virus-infected macrophages and endothelial cells (ECs), the site of replication and target for vascular pathology, respectively, the AP is activated. The AP activation, reduced FH and vascular leakage seen in dengue disease in part parallels other complement AP pathologies associated with FH deficiency, such as atypical haemolytic uraemic syndrome (aHUS). aHUS can be therapeutically targeted with inhibitors of complement terminal activity, raising the idea that strategies such as inhibition of complement or delivery of FH or other complement regulatory components to EC may be beneficial to combat the vascular leakage seen in severe dengue.

Original languageEnglish
Pages (from-to)2543-2555
Number of pages13
JournalFEBS Letters
Volume594
Issue number16
Early online date14 Jan 2020
DOIs
Publication statusPublished - 1 Aug 2020

Keywords

  • alternative pathway
  • complement
  • complement factor B
  • complement factor H
  • dengue virus

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    Carr, J. M., Cabezas-Falcon, S., Dubowsky, J. G., Hulme-Jones, J., & Gordon, D. L. (2020). Dengue virus and the complement alternative pathway. FEBS Letters, 594(16), 2543-2555. https://doi.org/10.1002/1873-3468.13730