Divergent coronaviruses discovered in the virome of lamprey with reddening syndrome

ABSTRACT Lamprey reddening syndrome (LRS) is an emerging disease affecting pouched lamprey ( Geotria australis ; kanakana/piharau), a culturally and ecologically significant species in Aotearoa, New Zealand. Characterized by skin hemorrhaging and elevated mortality, the etiology of LRS has remained unresolved despite previous investigations. We used a metatranscriptomic approach to characterize viral communities in 28 lamprey from New Zealand and Tasmania, Australia, comparing diseased and presumably healthy individuals. This analysis revealed eight fish-infecting RNA viruses, seven of which were novel, including two highly divergent coronaviruses. One of these coronaviruses possessed a bisegmented genome structure, and three lamprey were co-infected with both coronaviruses. While these coronaviruses were detected in both healthy and diseased individuals, lamprey with reddening exhibited markedly higher viral abundance, driven by elevated RNA transcripts of both viruses. This pattern suggests that increased coronavirus replication in diseased individuals may be influenced by host stress to environmental factors, or co-infection with other pathogens, rather than acting as a sole causative agent of disease. Beyond identifying candidate viral associations, this study expands the known virosphere of an ancient vertebrate lineage and demonstrates the utility of genomics-informed diagnostics for investigating disease in threatened wildlife. IMPORTANCE Lamprey are among the world's oldest living vertebrates and hold deep cultural significance for Māori as taonga species. An emerging disease causing skin reddening and death has raised concerns for their long-term conservation, but its cause has remained unknown. By applying genomic sequencing, we discovered a remarkable diversity of previously unknown viruses, including two highly unusual coronaviruses, in New Zealand and Australian lamprey. Rather than identifying a single disease-causing virus, our results suggest that disease is more likely associated with increased viral replication in stressed animals or with multiple infections acting together. These findings provide an important step toward understanding the health of this threatened species while also revealing unexpected viral diversity in an ancient vertebrate lineage. More broadly, the study demonstrates how genomics-informed diagnostics can help investigate unexplained disease outbreaks in wildlife and guide conservation management.