Recovery of plants from virus-induced symptoms is often described as a consequence of RNA silencing, an antiviral defense mechanism. For example, recovery of Nicotiana clevelandii from a nepovirus (tomato black ring virus) is associated with a decreased viral RNA concentration and sequence-specific resistance to further virus infection. In this study, we have characterized the interaction of another nepovirus, tomato ringspot virus (ToRSV), with host defense responses during symptom induction and subsequent recovery. Early in infection, ToRSV induced a necrotic phenotype in Nicotiana benthamiana that showed characteristics typical of a hypersensitive response. RNA silencing was also activated during ToRSV infection, as evidenced by the presence of ToRSV-derived small interfering RNAs (siRNAs) that could direct degradation of ToRSV sequences introduced into sensor constructs. Surprisingly, disappearance of symptoms was not accompanied by a commensurate reduction in viral RNA levels. The stability of ToRSV RNA after recovery was also observed in N. clevelandii and Cucumis sativus and in N. benthamiana plants carrying a functional RNA-dependent RNA polymerase 1 ortholog from Medicago truncatula. In experiments with a reporter transgene (green fluorescent protein), ToRSV did not suppress the initiation or maintenance of transgene silencing, although the movement of the silencing signal was partially hindered. Our results demonstrate that although RNA silencing is active during recovery, reduction of virus titer is not required for the initiation of this phenotype. This scenario adds an unforeseen layer of complexity to the interaction of nepoviruses with the host RNA silencing machinery. The possibility that viral proteins, viral RNAs, and/or virusderived siRNAs inactivate host defense responses is discussed.RNA silencing is an innate and ubiquitous defense mechanism that is activated by double-stranded RNAs (dsRNAs) and has been implicated in antiviral defense (6,7,60,61). The vast majority of plant viruses possess a positive-sense singlestranded RNA genome that is replicated through dsRNA intermediates (31). In addition, folding of self-complementary stretches within the single-stranded RNA genome allows the formation of stem-loop structures, which provide local regions of dsRNA (66). Once detected by the surveillance machinery of the plant cell, viral dsRNAs are cleaved by dicer-like (DCL) RNase III enzymes into 21-to 24-nucleotide (nt) small interfering RNAs (siRNAs) (20,23,59). The siRNAs guide RNAinduced silencing complexes (RISCs) to the target RNA in a sequence-specific manner (61). The target RNA is then cleaved by argonaute (AGO) proteins, which are RNase H-like enzymes and are associated with the RISC (9, 74). In addition, host RNA-dependent RNA polymerases (RDRs) have been proposed to play a crucial role in amplifying the RNA silencing signal (5,8,60,65). They bind the cleaved fragment released by RISC and produce a new generation of dsRNAs. This is probably followed by a new round of dicer cleavage to p...