Antibody-dependent enhancement of adeno-associated virus infection of human monocytic cell lines

In host animals, adeno-associated virus (AAV) is detectable mainly in the lymphoid tissue, which appears to be a target in natural infection. We used the human monocytic cell lines THP-1 and U937 to study the effect of mouse anti-AAV2 antiserum on infection with an AAV2 vector having the luciferase gene (AAV2/Luc). AAV2/Luc was found to infect THP-1 and U937 cells much less efficiently than HeLa cells, as monitored with the induced enzyme activity. Pre-incubation of AAV2/Luc with anti-AAV2 antiserum at a sub-neutralizing concentration enhanced by 2-to-10 fold infection of THP-1 and U937 with AAV2/Luc, but not of HeLa. Similarly, anti-AAV10 serum at a low level enhanced infection of THP-1 with AAV10/Luc. Sera of two cynomolgus monkeys, which had been probably infected with an AAV2-like virus, enhanced infection of THP-1 with AAV2/Luc. The enhancement was reduced with blocking the IgG-receptors Fcγ-RI and Fcγ-RII, which were displayed on the surface of THP-1 and U937 but not HeLa cells, with anti-Fcγ-RI antibody or anti-Fcγ-RII antibody. The data indicate that infection of Fcγ receptor-bearing cells with AAV is enhanced by anti-AAV IgG antibodies at a sub-neutralizing concentration that play a role in linking AAV particles and Fcγ receptors.