Blockade of the C5a–C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV

Jiang, Yuting; Zhao, Guangyu; Song, Nianping; Li, Pei; Chen, Yuehong; Guo, Yan; Li, Junfeng; Du, Lanying; Jiang, Shibo; Guo, Renfeng; Sun, Shihui; Zhou, Yusen

Complement functions as an immune surveillance system that rapidly responds to viral infection and plays a pivotal role in inflammatory responses. Compared to patients with dengue fever (DF), severely ill patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome have been shown to have higher levels of C3 cleavage products, specifically fD, which cleaves fB to yield the active (C3bBb) C3 convertase, and lower levels of fH, which inactivates the C3 convertase [31] [32] [33] . In addition, high levels of C3a, C5a, and sC5b-9 were observed to be present before plasma leakage occurred in DHF patients 34 . Moreover, expression of the complement inhibitor CD59-encoding gene was up-regulated more strongly in peripheral blood mononuclear cells from DF patients than in DHF patients 35 . These studies implicated the role of the complement system in the pathogenesis of severe forms of Dengue virus-associated diseases. In a Ross River virus (RRV)-induced complement-deficient mouse model, less severe tissue damage and disease symptoms following RRV infection also indicated an important role of complement in the RRV-induced pathogenesis 36 . In our previous study on highly pathogenic H5N1 influenza virus infection, dysregulated complement activation was observed to be accompanied by severe lung damage, which suggested that aberrant complement regulation may be an important causative factor after H5N1 virus infection 25 .