Thiamine (vitamin B1) biosynthesis involves key enzymes known as thiazole moieties (THI1/THI2), which have been shown to participate in plant responses to abiotic stress. However, the role of THI1/THI2 in plant immunity remains unclear. In this study, we cloned TaTHI2 from wheat and investigated its function in Chinese wheat mosaic virus (CWMV) infection. Overexpression of TaTHI2 (TaTHI2-OE) inhibited CWMV infection, while TaTHI2 silencing enhanced viral infection in wheat. Interestingly, the membrane-localized TaTHI2 protein was increased during CWMV infection. TaTHI2 also interacted with the Ca 2+ -dependent protein kinase 5 (TaCPK5), which is localized in the plasma membrane, and promoted reactive oxygen species (ROS) production by repressing TaCPK5-mediated activity of the catalase protein TaCAT1. CWMV CP disrupted the interaction between TaTHI2 and TaCAT1, reducing ROS accumulation and facilitating viral infection. Additionally, transgenic plants overexpressing TaTHI2 showed increased seed number per ear and 1000-kernel weight compared to control plants. Our findings reveal a novel function of TaTHI2 in plant immunity and suggest its potential as a valuable gene for balancing disease resistance and wheat yield. Furthermore, the disruption of the TaTHI2-mediated plant immune pathway by CWMV CP provides further evidence for the evolutionary arms race between plants and viruses.