Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2018

The complement alternative pathway: another contributor to dengue virus-induced vascular leak.  (#113)

Jillian Carr 1 , Sheila Cabezas 1 , David L Gordon 1
  1. Flinders University, BEDFORD, SA, Australia

The complement system is an important part of the body’s innate response to pathogens but needs to be tightly regulated to prevent host tissue damage. The severity of dengue disease has been linked to overactivity of the complement system, in particular the constitutively active alternative pathway (AP). A major negative regulator of AP activity is factor H (FH) while factor B (FB) promotes AP activity.


Through in vitro studies in primary cells we have shown that DENV infection induces AP activity, particularly at the endothelial cell (EC) surface and with properties that are likely to lead to complement-mediated EC permeability: a hallmark of severe dengue disease1. We have further investigated the AP in vivo, through analysis of patient samples and in the AG129-dengue virus (DENV) mouse model, with the latter a difficult model to interpret due to the interferon (IFN)-dependency of FH and FB production during DENV infection.


Overall, it is clear that the complement AP responds to DENV infection in a manner predicted to be deleterious to the endothelium and adding another layer of complexity to the pathogenesis of dengue vascular leak syndrome. Deciphering how we can address this for therapeutic benefit is of future interest.

  1. Cabezas, S., Bracho, G., Aloia, A. L., Adamson, P. J., Bonder, C. S., Smith, J. R., Gordon, D. L. and Carr, J. M. (2018) Dengue virus induces increased activity of the complement alternative pathway in infected cells. Journal of Virology (accepted May 2018).