Viral diseases affect grapevine cultures without inducing any resistance response. Thus, these plants develop systemic diseases and are chronically infected. Molecular events associated with viral compatible infections responsible for disease establishment and symptoms development are poorly understood. In this study, we surveyed viral infection in grapevines at a transcriptional level. Gene expression in the Vitis vinifera red wine cultivars Carménère and Cabernet-Sauvignon naturally infected with GLRaV-3 were evaluated using a genome-wide expression profiling with the Vitis vinifera GeneChip® from Affymetrix. We describe numerous genes that are induced or repressed in viral infected grapevines leaves. Changes in gene expression involved a wide spectrum of biological functions, including processes of translation and protein targeting, metabolism, transport, and cell defense. Considering cellular localization, the membrane and endomembrane systems appeared with the highest number of induced genes, while chloroplastic genes were mostly repressed. As most induced genes associated with the membranous system are involved in transport, the possible effect of virus in this process is discussed. Responses of both cultivars are analyzed and the results are compared with published data from other species. This is the first study of global gene profiling in grapevine in response to viral infections using DNA microarray.