Depierreux, D. | bioRxiv Science

bioRxiv2025

Re-infection with SARS-CoV-2 is associated with increased antibody breadth and potency against diverse sarbecovirus strains

The ease with which emerging SARS-CoV-2 variants escape neutralizing antibodies limits protection afforded by a prior exposure, be it infection or vaccination. While rare, broadly neutralizing antibodies with activity towards diverse sarbecoviruses have been detected in convalescent serum. Motivated by findings that plasma responses show increased neutralization breadth and potency with continued antigen exposure, we isolated monoclonal antibodies (mAbs) after a SARS-CoV-2 re-infection and compared them to those isolated one year prior, after the first breakthrough infection. Among clonal lineage members identified at both time points, mAbs from the later time point showed improved neutralization potency and breadth. One mAb isolated after re-infection, C68.490, targets a conserved region in the receptor binding domain core and shows remarkable activity not only against SARS-CoV-2 variants, but also diverse sarbecoviruses from more distant clades present in animal reservoirs. These findings suggest that a focus on individuals with diverse and repeated antigen exposure could lead to identification of antibodies with therapeutic utility not just towards current and future SARS-CoV-2 variants, but also distant sarbecoviruses in the event of a future spillover.

immunology↗

bioRxiv2019

A Novel Taxon of RNA Viruses Endemic to Planarian Flatworms

The phylum Platyhelminthes is composed of both parasitic and non-parasitic flatworms. While the parasitic species have drawn attention for their wide effects on human and livestock heath, free-living flatworms, such as freshwater planarians, have become molecular models of regeneration and stem cell biology in the laboratory. However, one aspect of planarian biology that remains understudied is the relationship between host and any endemic viruses. Here we used searches of multiple transcriptomes from Schmidtea mediterranea asexual strain CIW4 and detected a novel, double-stranded RNA (dsRNA) virus, named S. mediterranea tricladivirus (SmedTV), which represents a distinct taxon (proposed new genus) within a larger taxon of monosegmented dsRNA viruses of diverse hosts. Experimental evidence for SmedTV in S. mediterranea CIW4 was obtained through whole-mount in situ hybridization (WISH). SmedTV "expression" (detected by both sense and anti-sense probes) was discrete yet variable from worm to worm and cell type to cell type, suggesting a persistent infection. Single-cell RNA sequencing (scRNAseq) further supported that SmedTV expression was low in stem cells, but substantially higher in multiple, though not all, differentiated tissues, with notable neural enrichment. Interestingly, knockdown of SmedTV by RNA-interference resulted in a "cure" of SmedTV after 10 RNAi doses, and expression remained undetectable by WISH even after 90 days. Due to being able to evade host defenses and the endogenous RNAi pathway, we believe SmedTV represents a novel animal model to study host-virus evolution. Statement of significancePlanarians are freshwater flatworms and emerging models to study the molecular mechanisms of adult stem cell and regenerative biology. However, they also live in aquatic environments with high amounts of viruses, bacteria, fungi, and protist pathogens. How the planarian immune system copes with all of these is largely unknown and only 2 types of virus have been described. Here we find a novel dsRNA virus, endemic to multiple types of flatworms. We show that it is a persistent infection, and likely transmits from stem cell to differentiated cell in the planarian, while avoiding endogenous RNA-interference machinery and mechanisms used to suppress viruses. We present this as a new model to study host-virus defense and evolution.

microbiology↗