Activation of the complement cascade and generation of the C4b and C4a fragments yields two hypotheses of how Ad5 neutralization could occur: either liberation of the C4a fragment could act on target cells and render them less permissive to Ad5 infection or generation of the highly reactive thioester C4b results in C4b deposition on the virus, impacting its ability to productively infect. This evidence concerns the gene PSEN2 and infection.