The interplay between Caenorhabditis elegans larval development and Orsay virus infection

Caenorhabditis elegans development can be altered by its interactions with pathogens, such as bacteria1,2 or fungi3. However, the impact of viral infections on the nematodes development remains largely unexplored, and conversely, whether molting periods affect viral replication is unknown. Studying infections with Orsay virus (OrV), the only known natural C. elegans virus4, we investigated the role of molting on virus replication dynamics and the impact of OrV infection on C. elegans larval development. We found that OrV replicates during C. elegans molting periods. Indeed, nematodes inoculated near molt initiation exhibited higher OrV viral loads and the virus infected more intestinal cells. Moreover, nematodes inoculated right after hatching accelerated the start of the first molt and lengthened the second larval stage, effectively resynchronizing normal developmental timing. Overall, our work enhances understanding of OrV dynamics in C. elegans and elucidates the interplay between viral infection and nematode development. HIGHLIGHTSO_LIrsay virus replication peaks during molting periods, with larvae acquiring virus later in the first larval stage producing higher viral loads and more widespread intestinal infection than larvae acquiring it right after hatching. C_LIO_LIinfection alters the expression of key developmental regulators, particularly those with oscillatory profiles synchronized with molting cycles (such as let-7, lin-42 and nhr-23). C_LIO_LInematodes display temporal plasticity in development: accelerating the first molt while extending the second larval stage, ultimately resynchronizing their developmental timeline. C_LIO_LIis a bidirectional interaction between Orsay virus infection and C. elegans development: molting appears to transiently weaken antiviral defenses, while host development adapts to infection through temporal plasticity. C_LI