A virus-encoded protein suppresses methylation of the viral genome through its interaction with AGO4 in the Cajal body

Liping Wang,Yi Ding,Li He,Guiping Zhang,Jian‐Kang Zhu,Rosa Lozano-Durán

Published 2019 in bioRxiv

ABSTRACT

DNA methylation is a eukaryotic anti-viral defence mechanism. In plants, establishment of de novo DNA methylation is regulated by the RNA-directed DNA methylation pathway, which requires AGO4 function. The genome of the plant DNA viruses geminiviruses replicates in the nuclei of infected cells through not yet fully understood mechanisms and is subjected to methylation, a modification that negatively impacts infectivity. In Tomato yellow leaf curl virus, the virus-encoded V2 protein suppresses methylation of the viral DNA. Here, we identify AGO4 as a physical interactor of V2. AGO4 mediates methylation of the viral genome, which is countered by V2. Accordingly, virulence of a V2 mutant virus is partially restored by AGO4 silencing, hinting at the inhibition of AGO4 as a crucial virulence function of V2. Virus-produced V2 does not affect accumulation of viral small interfering RNA nor prevents their loading into AGO4, but impairs binding of this protein to the viral DNA. Importantly, the association between V2 and AGO4 occurs in the Cajal body, uncovering this subnuclear compartment as a crucial site in the viral cycle.

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