Viral small interfering RNAs target host genes to mediate disease symptoms in plants

The cucumber mosaic virus (cmv) y-satellite rna (y-sat) has a small non-protein-coding rna genome that induces yellowing symptoms in infected nicotiana tabacum (tobacco). how this rna pathogen induces such symptoms has been a longstanding question. we show that the yellowing symptoms are a result of small interfering rna (sirna)-directed rna silencing of the chlorophyll biosynthetic gene,chli. the chli mrna contains a 22-nucleotide (nt) complementary sequence to the y-sat genome,and in y-sat-infected plants,chli expression is dramatically down-regulated. small rna sequencing and 5′ race analyses confirmed that this 22-nt sequence was targeted for mrna cleavage by y-sat-derived sirnas. transformation of tobacco with a rna interference (rnai) vector targeting chli induced y-sat-like symptoms. in addition,the symptoms of y-sat infection can be completely prevented by transforming tobacco with a silencing-resistant variant of the chli gene. these results suggest that sirna-directed silencing of chli is solely responsible for the y-sat-induced symptoms. furthermore,we demonstrate that two nicotiana species,which do not develop yellowing symptoms upon y-sat infection,contain a single nucleotide polymorphism within the sirna-targeted chli sequence. this suggests that the previously observed species specificity of y-sat-induced symptoms is due to natural sequence variation in the chli gene,preventing chli silencing in species with a mismatch to the y-sat sirna. taken together,these findings provide the first demonstration of small rna-mediated viral disease symptom production and offer an explanation of the species specificity of the viral disease. © 2011 smith et al.