Disconnected Interacting Protein 1 (DIP1) is a dsRNA-binding protein that participates in a wide range of cellular processes. Whether DIP1 is involved in innate immunity remains unclear. Here, DIP1 was found to play an antiviral role in S2 cells. Its antiviral action is specific for DCV infection and not for DXV infection. dip1 mutant flies are hypersensitive to DCV infection. The increased mortality in dip1 mutant flies is associated with the accumulation of DCV positive-stranded RNAs in vivo. This study demonstrated that dip1 is a novel antiviral gene that restricts DCV replication in vitro and in vivo. (C) 2015 The Authors. Published by Elsevier Inc.