Dengue virus and the complement alternative pathway

FEBS Letters

article

Jillian M. Carr¹  Sheila Cabezas-Falcon¹  Joshua G. Dubowsky¹  Jarrod Hulme-Jones¹  David L. Gordon¹ 

[1] College of Medicine and Public Health, Flinders University;TGR Biosciences;Flinders Medical Centre

关键词: alternative pathway;    complement;    complement factor B;    complement factor H;    dengue virus;   

DOI  :  10.1002/1873-3468.13730

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown