TransVir

Horizontal transfer (HT) of genetic material is the transmission of DNA between organisms by means other than reproduction. Hundreds of such transfers have recently been uncovered in animals and it is now becoming clear that HT has an important impact on animal genome evolution. Yet, the vectors and mechanisms underlying HT between animals are still poorly known. In this project we will carry out the first systematic study of HT from animal host-to-virus in order to characterize the mechanisms involved in these transfers and assess their frequency during the course of a viral infection. We will also use experimental evolution to recapitulate virus-mediated HT between animals. The project is divided in three independent but complementary work packages (WP), each aiming at deciphering one or several aspects of a successful virus-mediated HT event. In WP1we will use a population genomics approach to identify junctions between virus and host genomes in ultra-deep sequencing datasets of virus genomes sequenced at depths >100,000X after in vivo infections of various host species. We will apply our approach to populations of two large double stranded DNA viruses: the Autographa californica Multiple NucleoPolyhedroVirus (AcMNPV) baculovirus, obtained after infections of four species of lepidopterans and the invertebrate iridescent virus (IIV iridovirus) obtained after infections of a fly and of a terrestrial isopod crustacean. In WP2 we will first assess the frequency of virus-to-host germline HT using a recombinant AcMNPV containing a moth transposable element capable of jumping from the virus to its host genome. Based on the results of this experiment we will then recapitulate events of donor-to-virus-to-receiver HT using wild type viruses. In WP3 we will characterize the mechanisms and factors influencing virus-mediated HT between animals. Specifically we will use RNA-seq of infected host species to test the hypothesis according to which the stress generated by viral infections unleashed the activity of host transposable elements, which tend to integrate more than other sequences into viral genomes. This project will characterize the full spectrum of host sequences that can become integrated in viral genomes during in vivo infections of animal hosts. In terms of basic science, we will make crucial advances in our understanding of HT between animals, of animal and viral genome evolution, and of the interactions between viruses and their animal hosts. In addition, baculoviruses are being used/developed as tools in various biological pest control strategies and in medical treatments such as gene therapy. The possibility that baculovirus-based applications are accompanied by high levels of baculovirus-mediated HT between the species in which a baculovirus-based vector was produced (moth cell lines or larvae) and a target species (the same or a different insect species in the wild for biopesticides; human for gene vectors) has never been considered nor investigated. Our project will therefore also have important consequences in terms of applied research as it will provide a solid basis for further evaluating the safety of baculoviruses as tools in biotechnological applications.