The tobacco N gene, a member of the Toll-interleukin 1 homology region/nucleotide binding site/leucine-rich repeat (TIR-NBS-LRR) class of resistance (R) genes, confers resistance to tobacco mosaic virus (TMV). We used a candidate gene approach to identify known defense genes that were also involved in N signaling. The requirement for these genes was determined by downregulating their expression using the well-established tobacco rattle virus (TRV)-based virus-induced gene silencing (VIGS). Silencing of genes encoding a mitogen-activated protein kinase (MAPK) NTF6/NRK1, or an MAPK kinase (MAPKK) MEK1/NQK1, attenuated N-mediated resistance to TMV. We also found that N resistance is compromised in plants in which expression of WRKY1-WRKY3 and MYB1 transcription factors were downregulated. In addition, suppression of jasmonic acid (JA) signaling component COI1 ortholog affected N function. However, downregulation of expression of CTR1 ortholog leads to more rapid hypersensitive response (HR). The involvement of these genes in N- and other R-gene-mediated defense provides further evidence for the convergence of downstream signaling pathways of different R genes.