Story of an infection: Viral dynamics and host responses in the <i>Caenorhabditis elegans</i> –Orsay virus pathosystem

Orsay virus (OrV) is the only known natural virus affecting <i>Caenorhabditis elegans</i>, with minimal impact on the animal's fitness due to its robust innate immune response. This study aimed to understand the interactions between <i>C. elegans</i> and OrV by tracking the infection's progression during larval development. Four distinct stages of infection were identified on the basis of viral load, with a peak in capsid-encoding RNA2 coinciding with the first signs of viral egression. Transcriptomic analysis revealed temporal changes in gene expression and functions induced by the infection. A specific set of up-regulated genes remained active throughout the infection, and genes correlated and anticorrelated with virus accumulation were identified. Responses to OrV mirrored reactions to other biotic stressors, distinguishing between virus-specific responses and broader immune responses. Moreover, mutants of early response genes and defense-related processes showed altered viral load progression, uncovering additional players in the antiviral defense response.