The upside-down jellyfish Cassiopea xamachana (Scyphozoa: Rhizostomeae) has been predominantly studied to understand its interaction with the endosymbiotic dinoflagellate algae Symbiodinium. As an easily culturable and tractable cnidarian model, it is an attractive alternative to stony corals to understanding the mechanisms driving establishment and maintenance of symbiosis. Cassiopea is also unique in requiring the symbiont in order to complete its transition to the adult stage, thereby providing an excellent model to understand symbiosis-driven development and evolution. Recently, the Cassiopea research system has gained interest beyond symbiosis in fields related to embryology, climate ecology, behavior, and more. With these developments, resources including genomes, transcriptomes, and laboratory protocols are steadily increasing. This review provides an overview of the broad range of interdisciplinary research that has utilized the Cassiopea model and highlights the advantages of using the model for future research.

The main viral protease (3CL^pro) is indispensable for SARS-CoV-2 replication. We delineate the human protein substrate landscape of 3CL^pro by TAILS substrate-targeted N-terminomics. We identify more than 100 substrates in human lung and kidney cells supported by analyses of SARS-CoV-2-infected cells. Enzyme kinetics and molecular docking simulations of 3CL^pro engaging substrates reveal how noncanonical cleavage sites, which diverge from SARS-CoV, guide substrate specificity. Cleaving the interactors of essential effector proteins, effectively stranding them from their binding partners, amplifies the consequences of proteolysis. We show that 3CL^pro targets the Hippo pathway, including inactivation of MAP4K5, and key effectors of transcription, mRNA processing, and translation. We demonstrate that Spike glycoprotein directly binds galectin-8, with galectin-8 cleavage disengaging CALCOCO2/NDP52 to decouple antiviral-autophagy. Indeed, in post-mortem COVID-19 lung samples, NDP52 rarely colocalizes with galectin-8, unlike in healthy lungs. The 3CL^pro substrate degradome establishes a foundational substrate atlas to accelerate exploration of SARS-CoV-2 pathology and drug design.

Very little is known about aquatic RNA virus populations and genome evolution. This is the first study that analyzes marine environmental RNA viral assemblages in an evolutionary and broad geographical context. This study contributes the largest marine RNA virus metagenomic data set to date, substantially increasing the sequencing space for RNA viruses and also providing a baseline for comparisons of marine RNA virus diversity. The new viruses discovered in this study are representative of the most abundant family of marine RNA viruses, theMarnaviridae, and expand our view of the diversity of this important group. Overall, our data and analyses provide a foundation for interpreting marine RNA virus diversity and evolution.

The family Marnaviridae comprises small non-enveloped viruses with positive-sense RNA genomes of 8.6–9.6 kb. Isolates infect marine single-celled eukaryotes (protists) that come from diverse lineages. Some members are known from metagenomic studies of ocean virioplankton, with additional unclassified viruses described from metagenomic datasets derived from marine and freshwater environments. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Marnaviridae, which is available at ictv.global/report/marnaviridae.

Myocarditis, inflammation of the heart muscle, affects all demographics and is a major cause of sudden and unexpected death in young people. It is most commonly caused by viral infections of the heart, with coxsackievirus B3 (CVB3) being among the most prevalent pathogens. To understand the molecular pathogenesis of CVB3 infection and provide strategies for developing treatments, we examined the role of a key nuclear pore protein 98 (NUP98) in the setting of viral myocarditis. NUP98 was cleaved as early as 2 h post-CVB3 infection. This cleavage was further verified through both the ectopic expression of viral proteases and in vitro using purified recombinant CVB3 proteases (2A and 3C), which demonstrated that CVB3 2A but not 3C is responsible for this cleavage. By immunostaining and confocal imaging, we observed that cleavage resulted in the redistribution of NUP98 to punctate structures in the cytoplasm. Targeted siRNA knockdown of NUP98 during infection further increased viral protein expression and viral titer, and reduced cell viability, suggesting a potential antiviral role of NUP98. Moreover, we discovered that expression levels of neuregulin-1 (NRG1), a cardioprotective gene, and presenilin-1 (PSEN1), a cellular protease processing the tyrosine kinase receptor ERBB4 of NRG1, were reliant upon NUP98 and were downregulated during CVB3 infection. In addition, expression of these NUP98 target genes in myocardium tissue not only occurred at an earlier phase of infection, but also appeared in areas away from the initial inflammatory regions. Collectively, CVB3-induced cleavage of NUP98 and subsequent impairment of the cardioprotective NRG1-ERBB4/PSEN1 signaling cascade may contribute to increased myocardial damage in the context of CVB3-induced myocarditis. To our knowledge, this is the first study to demonstrate the link between NUP98 and the NRG1 signaling pathway in viral myocarditis.