Interactions of viruses and the humoral innate immune response

The innate immune response is crucial for defense against virus infections where the complement system, coagulation cascade and natural antibodies play key roles. These immune components are interconnected in an intricate network and are tightly regulated to maintain homeostasis and avoid uncontrolled immune responses. Many viruses in turn have evolved to modulate these interactions through various strategies to evade innate immune activation. This review summarizes the current understanding on viral strategies to inhibit the activation of complement and coagulation cascades, evade natural antibody-mediated clearance and utilize complement regulatory mechanisms to their advantage. •Viruses inhibit complement activation by protease degradation of initiators.•Viruses produce complement mimics or incorporate regulators into the virion to inhibit complement.•Natural antibodies aid in viral clearance but viruses also inhibit natural antibody recognition•Viruses may evade the coagulation pathway or even utilize it in pathogenesis.