Top-Tier Senior Analyst Review: Molecular Virology and Evolutionary Genomics
Reviewing Group: This topic is best reviewed by a panel of Principal Investigators in Viral Metagenomics and Evolutionary Biologists specializing in the "giant" virus-host interface.
Abstract:
This discussion, recorded at the Sixth Ringberg Symposium on Giant Viruses, details the discovery and characterization of Mirusviricota, a highly diverse and prevalent phylum of large double-stranded DNA viruses. These viruses exhibit a unique chimeric architecture: their virion morphogenesis module (including the HK97-fold major capsid protein) links them to the Duplodnaviria (herpesviruses and tailed bacteriophages), while their informational module (DNA/RNA polymerases) is homologous to the Nucleocytoviricota (giant viruses in the realm Varidnaviria).
The panel highlights significant findings in the marine protist Aurantiochytrium and brown algae (Ectocarpus), where mirusviruses exist as both circular episomes and chromosomal integrants. Genomic analysis reveals that major mirusvirus lineages (Okeanovirales and Styxvirales) are exceptionally rich in spliceosomal introns and lack independent replication machinery, indicating a specialized niche for reproduction within the host nucleus—a departure from the cytoplasmic replication typical of most giant viruses. The discussion further identifies "shintrons" (spliceosomal homing introns) encoding endonucleases and evidence of long-range trans-splicing in virion morphogenesis genes, suggesting a complex evolutionary transition between cytoplasmic and nuclear life cycles.
Comprehensive Summary of TWiV 1281
0:30 Sixth Ringberg Symposium: Vincent Racaniello hosts John Archibald (Dalhousie University), Susana Coelho (Max Planck Institute), and Tom Delmont (CNRS/Genoscope) to discuss the emerging field of giant virus research in marine ecosystems.
11:34 Brown Algae (Ectocarpus) Genomics: Coelho explains that brown algae evolved multicellularity independently of plants and animals. Her lab’s study of Ectocarpus led to the "accidental" discovery of endogenous viral elements (EVEs) integrated into the algal genome.
19:11 Coordinated Viral Lifecycle: The Ectocarpus siliculosis virus replicates specifically in the gamitangia (reproductive structures). Instead of killing the host, the virus coordinates its release with the release of host gametes, effectively sterilizing the host to promote viral dispersal.
24:32 Temperature-Dependent Activation: Viral symptoms and particle production in Ectocarpus are induced by low temperatures (10°C) and are inhibited at higher temperatures (14–20°C), suggesting a fine-tuned evolutionary coordination between the host's intertidal environment and the viral lifecycle.
29:27 Discovery of Mirusviruses (Mirusviricota): Delmont describes the discovery of mirusviruses ("strange viruses") through Tara Oceans metagenomic data. These viruses are chimeric, possessing structural genes related to herpesviruses (Duplodnaviria) and informational genes related to giant viruses (Nucleocytoviricota).
33:08 Global Abundance: Metagenomic signals indicate mirusviruses are among the most abundant and active eukaryotic viruses in the sunlit oceans, infecting a broad range of unicellular eukaryotes (plankton) from pole to pole.
41:57Mirusvirus in Aurantiochytrium: Archibald details the discovery of mirusvirus elements in the marine protist Aurantiochytrium limacinum. The host harbors two distinct elements: an episomal form (V1) and a chromosomal integrant (V2) on chromosome 15.
47:41 Visualization and Morphology: Using transmission electron microscopy (TEM), the team identified hexagonal viral capsids (120–140 nm) maturing in the host nucleus and budding through the nuclear membrane, acquiring a tegument-like structure in the cytoplasm.
54:39 Historical Re-identification: The panel notes that "herpes-type" particles reported in fungi in 1972 were likely the first visual documentation of mirusviruses, long before metagenomics enabled their classification.
1:00:10 Genome-Resolved Metagenomics: Delmont explains the use of the anvi’o platform to extract high-quality metagenome-assembled genomes (MAGs). This allowed the identification of 1,257 non-redundant mirusvirus genomes, some exceeding 500 kb (giant virus status).
1:10:45 Nuclear Replication Evidence: Major mirusvirus orders (Okeanovirales and Styxvirales) lack DNA polymerase and are enriched with spliceosomal introns in late-expression structural genes. Since the spliceosome is located exclusively in the nucleus, these viruses are predicted to replicate in the host nucleus, relying on host machinery.
1:12:03 "Shintrons" and Endonucleases: Mirusvirus introns are found to harbor over 2,000 protein-coding genes, including homing endonucleases (HNH and GIY-YIG types). These "shintrons" appear to target essential virion morphogenesis genes, potentially facilitating their spread via homologous recombination.
1:14:44 Trans-Splicing in Terminase Genes: Researchers confirmed that the terminase gene (essential for DNA packaging) undergoes trans-splicing, where ATPase and nuclease domains encoded far apart in the genome are joined at the RNA level. This trait is shared with Alloherpesviruses.
1:20:00 Future Research Vectors: Ongoing work includes using CRISPR/Cas to knock out viral genes in Ectocarpus to understand their function and exploring coastline mirusvirus diversity through the TREC (Traversing European Coastlines) expedition.