ReviewViral regulators of complement activation: Structure, function and evolution

•Pox and herpesviruses encode homologs of human RCA proteins.•Electrostatics plays a crucial role in recognition & binding of vRCAs to target proteins.•Viral homologs of RCA proteins (vRCA) are involved in immune evasion.•vRCA studies are helping to understand novel aspects of the RCA protein family.

The complement system surveillance in the host is effective in controlling viral propagation. Consequently, to subvert this effector mechanism, viruses have developed a series of adaptations. One among these is encoding mimics of host regulators of complement activation (RCA) which help viruses to avoid being labeled as 'foreign' and protect them from complement-mediated neutralization and complement-enhanced antiviral adaptive immunity. In this review, we provide an overview on the structure, function and evolution of viral RCA proteins.