| Summary: | Among the numerous biological constraints that hinder cassava (<i>Manihot esculenta</i> Crantz) production, foremost is cassava mosaic disease (CMD) caused by virus members of the family <i>Geminiviridae</i>, genus <i>Begomovirus</i>. The mechanisms of CMD tolerance and susceptibility are not fully understood; however, CMD susceptible T200 and tolerant TME3 cassava landraces have been shown to exhibit different large-scale transcriptional reprogramming in response to South African cassava mosaic virus (SACMV). Recent identification of 85 MeWRKY transcription factors in cassava demonstrated high orthology with those in <i>Arabidopsis</i>, however, little is known about their roles in virus responses in this non-model crop. Significant differences in <i>MeWRKY</i> expression and regulatory networks between the T200 and TME3 landraces were demonstrated. Overall, WRKY expression and associated hormone and enriched biological processes in both landraces reflect oxidative and other biotic stress responses to SACMV. Notably, <i>MeWRKY11</i> and <i>MeWRKY81</i> were uniquely up and downregulated at 12 and 67 days post infection (dpi) respectively in TME3, implicating a role in tolerance and symptom recovery. AtWRKY28 and AtWRKY40 homologs of MeWRKY81 and MeWRKY11, respectively, have been shown to be involved in regulation of jasmonic and salicylic acid signaling in <i>Arabidopsis</i>. AtWRKY28 is an interactor in the RPW8-NBS resistance (R) protein network and downregulation of its homolog <i>MeWRKY81</i> at 67 dpi in TME3 suggests a negative role for this WRKY in SACMV tolerance. In contrast, in T200, nine <i>MeWRKY</i>s were differentially expressed from early (12 dpi), middle (32 dpi) to late (67 dpi) infection. <i>MeWRKY27</i> (homolog <i>AtWRKY</i>33) and <i>MeWRKY55</i> (homolog <i>AtWRKY53</i>) were uniquely up-regulated at 12, 32 and 67 dpi in T200. AtWRKY33 and AtWRKY53 are positive regulators of leaf senescence and oxidative stress in <i>Arabidopsis</i>, suggesting MeWRKY55 and 27 contribute to susceptibility in T200.
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