Single-cell-resolved natural giant virus infections reveal conserved protist immunity

Abstract Single-cell eukaryotes (protists) are key players in microbial ecosystems. Yet, our understanding of how they interact with viruses in nature and how antiviral defenses shape these relationships remains limited. Using a single-cell multi-omics approach, we mapped associations between giant viruses and their hosts and identified active giant-virus infections in an alpine lake protist community. In naturally infected dinoflagellates, infection was accompanied by the selective induction of viperin, an ancient antiviral enzyme conserved from bacteria to humans. We also observed virus-encoded homologs of immunity-related genes whose expression correlated with viperin expression, raising the possibility of a role in viral counter-defense. These findings reveal an ecological dimension of protist immunity and provide a framework for tracing the host-virus arms race across divergent cellular lineages.