Eukaryotic Translation Initiation Factor 2 Modulates the Expression of Midgut Receptors to Confer Resistance to <i>Bacillus thuringiensis</i> Cry1Ac Toxin in <i>Helicoverpa armigera</i>

Studying the insect resistance mechanism to <i>Bacillus thuringiensis</i> (Bt) is beneficial to address the ever-growing problem of evolved resistance. Previous RNaseq data indicated that a eukaryotic translation initiation factor 2 (eIF2) expression showed significant differences in Cry1Ac-resistant <i>Helicoverpa armigera</i> strains. We investigated HaeIF2's role in Cry1Ac resistance. Quantitative PCR (qPCR) confirmed that HaeIF2 expression was significantly downregulated in Cry1Ac-resistant <i>H. armigera</i> (BtR). Overexpression and RNAi in midgut cells and larvae showed that HaeIF2's expression affects susceptibility to Cry1Ac by modulating the expression of receptors CAD, ABCC2, and ABCC3. Further studies demonstrated that HaeIF2 activates receptor expression by binding to eIF2 sites in the promoter regions. The downregulated three receptors in the BtR consistent with reduced HaeIF2 levels suggest HaeIF2 is involved in Cry1Ac resistance. These findings reveal insect resistance to Cry1Ac is due to coordinated transcriptional regulation of receptor molecules in the BtR strain, further expanding our understanding of the molecular basis of insect resistance to Bt.