To investigate how rice responds to RSV infection, we integrated miRNA expression with parallel mRNA transcription profiling by deep sequencing. A total of 570 miRNAs were identified of which 69 miRNAs (56 up-regulated and 13 down-regulated) were significantly modified by RSV infection. Digital gene expression (DGE) analysis showed that 1274 mRNAs (431 up-regulated and 843 down-regulated genes) were differentially expressed by RSV infection. The differential expression of selected miRNAs and mRNAs was confirmed by qRT-PCR. Gene ontology (GO) and pathway enrichment analysis showed that a complex set of miRNA and mRNA networks were selectively regulated by RSV infection. In particular, 63 differentially expressed miRNAs were found to be significantly and negatively correlated with 160 target mRNAs. Interestingly, 22 up-regulated miRNAs were negatively correlated with 24 down-regulated mRNAs encoding disease resistance-related proteins, indicating that the host defense responses were selectively suppressed by RSV infection. The suppression of both osa-miR1423-5p- and osa-miR1870-5p-mediated resistance pathways was further confirmed by qRT-PCR. Chloroplast functions were also targeted by RSV, especially the zeaxanthin cycle, which would affect the stability of thylakoid membranes and the biosynthesis of ABA. All these modifications may contribute to viral symptom development and provide new insights into the pathogenicity mechanisms of RSV. Overall design: Examination of microRNAome and trascriptome in mock and RSV-infected rice plants.