Host genome integration and giant virus-induced reactivation of the virophage mavirus

Endogenous viral elements (EVEs) are increasingly found in eukaryotic genomes 1 , yet little is known about their origins, dynamics, or function. Here, we provide a compelling example of a DNA virus that readily integrates into a eukaryotic genome where it acts as an inducible antiviral defense system. We found that the virophage mavirus 2 , a parasite of the giant Cafeteria roenbergensis virus (CroV) 3 , integrates at multiple sites within the nuclear genome of the marine protozoan Cafeteria roenbergensis . The endogenous mavirus is structurally and genetically similar to the eukaryotic Maverick/Polinton DNA transposons 4,5 and endogenous polintoviruses 6 . Provirophage genes are not constitutively expressed, but are specifically activated by superinfection with CroV, which induces the production of infectious mavirus particles. Virophages inhibit the replication of giant viruses and a beneficial effect of provirophages on their host cells has been hypothesized 2,7 . We found that provirophage-carrying cells are not directly protected from CroV; however, lysis of these cells releases reactivated mavirus particles that are then able to suppress CroV replication and enhance host survival of other CroV-infected flagellate populations in a dose-dependent manner. The host-parasite interaction described here involves an altruistic aspect that is unique among microbes. Our results demonstrate a direct link between mavirus and Maverick/Polinton elements and suggest that provirophages can defend natural protist populations against infection by giant viruses.