Many viruses utilize host lipids during the viral life cycle. We used the novel C. elegans-Orsay virus experimental model to define the impact of virus infection on lipid abundance as well as the dependency of virus infection on host lipids. Lipid staining with Lipidtox in live animals demonstrated that by 24 hpi there was a reduction in lipid abundance of around 60 %. To analyze the dependence of Orsay virus on lipids, we genetically depleted
sbp-1, a transcription factor involved in the synthesis of lipids. RNAi knockdown of
sbp-1 reduced Orsay virus RNA levels by 200-fold. Likewise, mutant animals in this gene demonstrated a reduction of 1000-fold in the amount of viral RNA.
sbp-1 has been reported to regulate the expression of several enzymes involved in the synthesis of lipids. Mutants in
sbp-1 have reduced levels of oleic acid and increased accumulation of its precursor stearic acid. To analyze if we can recover the viral infection in
sbp-1 mutant animals, we supplemented the growth media with oleic acid. Orsay viral RNA levels were rescued to levels comparable to those found in wild type worms; addition of stearic acid had no effect. Likewise, to investigate what stage of virus infection was affected, an in vivo replicon system was generated in the
sbp-1mutant animals. Our findings suggest that an early step of virus infection subsequent to viral entry was inhibited. These data demonstrate the critical role of host lipids for virus infection in an in vivo model, providing a novel route to further dissect the interactions between lipids and viruses.