Yellow vein mosaic disease induced by a whitefly transmitted monopartite begomovirus causes a devastating foliar disease of Hibiscus cannabinus (mesta) crops across India. Characterization of the causal virus at molecular level and different epidemiological factors associated with the disease have already been investigated to understand the role of driving components behind continued spread of the disease. We have investigated the global gene expression profiling to increase knowledge of transcriptional changes taken place in a compatible interaction between Mesta yellow vein mosaic virus (MeYVMV) and H. cannabinus plants by PCR-based suppression subtractive hybridization supplemented with mirror orientation selection. Dot-blot analysis of forward and reverse subtracted libraries with respective cDNA probes confirmed the differential regulation of 100 clones of forward subtracted library and 70 clones of reverse-subtracted library of 220 positive colonies (proved by colony PCR and restriction release) picked for analysis (from both reactions), and these clones were sequenced. Sequence analysis and virtual Northern blot at varying time points of the infection process finally confirmed the consistent up-regulation of 11 and down-regulation of seven gene fragments (ESTs) in infected plant. The up-regulated transcripts could be functionally categorized in three different groups: (i) members of signal transduction cascades, (ii) host defence-responsive elements and (iii) factors involved in metabolism and transport. Down-regulation of the gene encoding SGT1 protein in infected plants suggested the possible modulation by the virus to overcome host defence responses. Other down-regulated ESTs were found to be members of photosynthetic pathways, electron transport chain and metabolism. Differential regulations of a few genes from both libraries were subsequently confirmed by Northern analysis. Our results present the first evidence of genes that might be involved in recognition and signalling routes in the mesta plant after infection with MeYVMV and facilitate the design of new crop protection strategies.