Adenosine Kinase is Inactivated by Geminivirus AL2 and L2 Proteins

AL2 and L2 are related proteins encoded by geminiviruses of the Begomovirus and Curtovirus genera, respectively. Both are pathogenicity determinants that cause enhanced susceptibility when expressed in transgenic plants. To understand how geminiviruses defeat host mechanisms that limit infectivity, we searched for cellular proteins that interact with AL2 and L2. Here, we present evidence that the viral proteins interact with and inactivate adenosine kinase (ADK), a nucleoside kinase that catalyzes the salvage synthesis of 5'-AMP from adenosine and ATP. We show that the AL2 and L2 proteins inactivate ADK in vitro and after coexpression in Escherichia coli and yeast. We also demonstrate that ADK activity is reduced in transgenic plants expressing the viral proteins and in geminivirus-infected plant tissues. By contrast, ADK activity is increased after inoculation of plants with diverse RNA viruses or a geminivirus lacking a functional L2 gene. Consistent with its ability to interact with multiple cellular kinases, we also demonstrate that AL2 is present in both the nucleus and the cytoplasm of infected plant cells. These data indicate that ADK is targeted by viral pathogens and provide evidence that this "housekeeping" enzyme might be a part of host defense responses. In previous work, we showed that AL2 and L2 also interact with and inactivate SNF1 kinase, a global regulator of metabolism that is activated by 5'-AMP. Together, these observations suggest that metabolic alterations mediated by SNF1 are an important component of innate antiviral defenses and that the inactivation of ADK and SNF1 by the geminivirus proteins represents a dual strategy to counter this defense. AL2 proteins also have been shown to act as suppressors of RNA silencing, an adaptive host defense response. A possible relationship between ADK inactivation and silencing suppression is discussed.