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 Fcgamma-RI and Fcgamma-RII, which were displayed on the surface of THP-1 and U937 but not HeLa cells, with anti-Fcgamma-RI antibody or anti-Fcgamma-RII antibody. The data indicate that infection of Fcgamma 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 Fcgamma receptors.
Mori
Seiichiro
S
Center for Pathogen Genomics, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Takeuchi
Takamasa
T
Kanda
Tadahito
T
D000818:Animals; D000914:Antibodies, Viral; D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D000229:Dependovirus / Q000254:growth & development*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008252:Macaca fascicularis; D051379:Mice; D009000:Monocytes / Q000821:virology*; D017452:Receptors, IgG / Q000037:antagonists & inhibitors; D013194:Staining and Labeling / Q000379:methods
D000914:Antibodies, Viral; D017452:Receptors, IgG; D008156:Luciferases