Cassava mosaic disease, caused by cassava bego- moviruses, is the most serious disease for cassava in Africa. However, the pathogenesis of this disease is poorly under- stood. We employed high throughput digital gene expression profiling based on the Illumina Solexa sequencing technology to investigate the global transcriptional response of cassava to African cassava mosaic virus infection. We found that 3,21o genes were differentially expressed in virus-infected cassava leaves. Gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that genes implicated in photosynthesis were most affected, consistent with the chlorotic symptoms observed in infected leaves. The upregu- lation of chlorophyll degradation genes, including the genes encoding chlorophyUase, pheophytinase, and pheophorbide a oxygenase, and downregulation of genes encoding the major apoproteins in light-harvesting complex II were confirmed by qRT-PCR. These findings, together with the reduction of chlorophyll b content and fewer grana stacks in the infected leaf cells, reveal that the degradation of chlorophyll plays an important role in A^rican cassava mosaic virus symptom development. This study will provide a road map for future investigations into viral pathogenesis.