Key role of the scavenger receptor MARCO in mediating adenovirus infection and subsequent innate responses of macrophages
Maler MD, Nielsen PJ, Stichling N, Cohen I, Ruzsics Z, Wood C, Engelhard P, Suomalainen M, Gyory I, Huber M, Müller-Quernheim J, Schamel WWA, Gordon S, Jakob T, Martin SF, Jahnen-Dechent W, Greber UF, Freudenberg MA, Fejer G
Adenoviral vectors will be increasingly used in synthetic biology approaches and gene therapy protocols. Despite this the receptor by which this virus enters macrophages remained unknown. In this BIOSS publication we asked whether the scavenger receptor MARCO might play this role. We show that adenovirus infection is significantly more efficient in MARCO-positive macrophages than in MARCO-negative macrophages. Furthermore, using antibodies blocking ligand binding to MARCO, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to virus recognition through the cytoplasmic DNA sensor cGAS. This leads to proinflammatory responses by the infected macrophages. These findings contribute to the understanding of viral pathogenesis in macrophages and opens new possibilities for synthetic biology approaches using adenovirus vectors.