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Plant viral diseases compromise the growth and yield of the crop globally, and they tend to be more serious under extreme temperatures and drought climate changes. Currently, regulatory dynamics during plant development and in response to virus infection at the plant cell level remain largely unknown. In this study, single‐cell RNA sequencing on 23 226 individual cells from healthy and tomato chlorosis virus‐infected leaves was established. The specific expression and epigenetic landscape of each cell type during the viral infection stage were depicted. Notably, the mesophyll cells showed a rapid function transition in virus‐infected leaves, which is consistent with the pathological changes such as thinner leaves and decreased chloroplast lamella in virus‐infected samples. Interestingly, the F‐box protein SKIP2 was identified to play a pivotal role in chlorophyll maintenance during virus infection in tomato …