Giardiavirus rewires host translation and glycolytic metabolism to support its replication in Giardia duodenalis

Giardia duodenalis is an intestinal protozoan parasite responsible for giardiasis, a disease primarily characterized by diarrhea and associated with long-term complications such as malnutrition and growth impairment in children. The presence of Giardiavirus (GLV) has been shown to attenuate pathological damage in G. duodenalis-infected murine models and modulate distinct pro-inflammatory responses in host cells stimulated by Giardia. However, the understanding of the impact of the GLV on the G. duodenalis itself remains limited. Here, we found that GLV infection interfered with the host protein expression system by reducing both mRNA and protein levels of Giardia genes, while paradoxically enhancing mRNA translation efficiency. Additionally, GLV infection induced energy metabolic reprogramming in Giardia, as evidenced by the identification of 21 significantly altered energy metabolites. KEGG enrichment analysis revealed glycolysis/gluconeogenesis as the most prominently enriched metabolic pathway in GLV-infected Giardia. Notably, glycolysis continued to be upregulated with successive passages of GLV infection, even after the GLV load plateaued. The glycolytic enzyme enolase was found to be closely associated with GLV infection within Giardia, and morpholino-mediated knockdown of enolase expression resulted in a significant reduction in GLV replication. Overall, these findings demonstrate that GLV infection manipulates host translation and energy metabolic pathways to facilitate its persistence in G. duodenalis, and reveal both GLV and host metabolic targets as promising research subjects for developing drugs and vaccines for the prevention and treatment of giardiasis.