Mechanisms of Complement Regulation of Infection by Flaviviruses

The complement system is a family of more than 30 serum proteins and cell surface receptors that recognizes pathogen-associated molecular patterns, altered-self ligands, and immune complexes. Complement activation through the classical, lectin and alternative pathways triggers an array of functions including direct pathogen opsonization and/or lysis, and enhancement of B and T cell responses. Recent work has demonstrated that complement activation is necessary for the development of protective immune responses and mediates important antiviral effector functions of Flavivirus-specific antibody. In this review, we will examine the mechanisms and functions of complement activation and discuss our current understanding of the role of complement in protection against infection by Flaviviruses, with an emphasis on experiments with West Nile virus (WNV). In addition, we will discuss ongoing studies on the immune evasion mechanisms that WNV uses to limit complement activation.