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Flaviviruses unexpectedly shut off host translation

It was a peer review request that got Alessia Ruggieri and her group at University of Heidelberg to look more closely at how Dengue virus manipulates the cellular translation and stress machineries during infection.

In a previous study, Ruggieri showed that Hepatitis C virus infection induced an oscillating stress response that correlated with phases in which host cell translation is switched off and then reactivated. She visualized cycles of assembly and disassembly of huge aggregates called stress granules in which stalled mRNA transcripts get bound up. The reviewers asked whether the closely related Dengue virus elicited the same type of stress response. It turned out that Dengue virus does it differently: no stress granules were seen at all. Dengue virus is a positive single-strand RNA virus, which has a genome that is capped with a similar structure to that of cellular mRNAs. This feature makes it dependent on active host translation—or so it was thought.
 
 

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