Ss in CD40L-/- mice, was ineffective in this case. Interactions between the viral capsid and complement have also been shown to play a role in the innate immune response to AAV (Zaiss et al., 2008). Immunoprecipitation studies showed that iC3b can bind to the AAV capsid, and that, in vitro, complement binding to AAV2 can increase capsid uptake and proinflammatory cytokine production by macrophages