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There is strong selection for the evolution of systems that protect bacterial populations from viral attack. We report a single phage defense protein, Hna, that provides protection against diverse phages in Sinorhizobium meliloti , a nitrogen-fixing alpha-proteobacterium. Homologs of Hna are distributed widely across bacterial lineages, and a homologous protein from Escherichia coli also confers phage defense. Hna contains superfamily II helicase motifs at its N terminus and a nuclease motif at its C terminus, with mutagenesis of these motifs inactivating viral defense. Hna variably impacts phage DNA replication but consistently triggers an abortive infection response in which infected cells carrying the system die but do not release phage progeny. A similar host cell response is triggered in cells containing Hna upon expression of a phage-encoded single-stranded DNA binding protein (SSB), independent of phage infection. Thus, we conclude that Hna limits phage spread by initiating abortive infection in response to a phage protein. [Display omitted] • The helicase/nuclease Hna confers defense against phages in Sinorhizobium meliloti • A homologous protein from Escherichia coli also has antiphage activity • Hna prevents phage propagation through an abortive infection mechanism • A phage single-stranded DNA binding protein triggers an Hna anti-host response Microorganisms have evolved a variety of systems to combat viral infection. Sather et al. describe a bacteriophage defense system ("Hna") consisting of a single predicted helicase/nuclease that confers protection by abortive infection. Homologs of Hna are present in a wide array of bacteria, including many medically or agriculturally relevant species. [ABSTRACT FROM AUTHOR]