Neutralization of endogenous interferon-beta increases the efficiency of adenoviral vector-mediated gene transduction.
One reason for low transduction efficiency and, hence, the inefficiency of gene therapy using adenoviral vectors may be the natural antiviral defense mechanisms of hosts. In this study, we investigated the effects of endogenous interferon-beta (IFN-beta) on gene transduction by adenoviral vectors. Infection of murine macrophages with Ad5CMV-LacZ produced increased expression of endogenous IFN-beta. Neutralization with anti-IFN-beta antibody (but not control immunoglobulin) during infection with the vector enhanced expression of LacZ. In contrast, IFN-beta gene expression was not detected in readily transduced NIH 3T3 cells, and the transduction efficiency of NIH 3T3 cells was unaffected by the antibody. LacZ gene expression in NIH 3T3 cells was decreased when cocultured with macrophages or in the presence of exogenous IFN-beta. The addition of the anti-IFN-beta antibody reversed this inhibition. These results demonstrate that IFN-beta-mediated cellular antiviral mechanisms are a barrier to gene transduction by adenoviral vectors.
Dong
Z
Z
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston, USA.
Yang
X
X
Fidler
I J
IJ
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005822:Genetic Vectors; D007369:Interferon Inducers; D016899:Interferon-beta / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014161:Transduction, Genetic
D000998:Antiviral Agents; D007369:Interferon Inducers; D016899:Interferon-beta