HHV-6A miR-aU14 and miR-30c alteration

Published: 15 February 2022| Version 3 | DOI: 10.17632/grnz4krxp2.3
Bhupesh Prusty


Raw data for the manuscript showing HHV-6A encoded miR-aU14 mediated miR-30c regulation. Manuscript title: Selective inhibition of microRNA processing by a herpesvirus-encoded microRNA governs virus reactivation from latency Summary: Many viruses encode their own suite of miRNAs, which typically lack sequence homology to the miRNAs of their hosts. The molecular mechanisms and targets of virus-encoded miRNAs are incompletely understood. Here, we identify miRNA-mediated inhibition of miRNA processing as a general cellular mechanism that Human Herpesvirus 6A (HHV-6A) exploits to evade intrinsic host defense and drive the latent-lytic switch. We show that the most abundant HHV-6A miRNA (miR-aU14) selectively inhibits miRNA processing of miR-30 family members through direct RNA:RNA interaction. The subsequent loss of mature miR-30 results in a profound disruption of mitochondrial architecture via the miR-30/p53/Drp1 axis. This impairs type I interferon responses and promotes productive infection. Ectopic expression of miR-aU14 was sufficient and necessary to trigger virus reactivation from latency. Finally, we demonstrate that miRNA-mediated inhibition of miRNA processing represents a general mechanism in the cellular regulatory network that can be exploited to selectively target individual members of miRNA gene families.



Julius-Maximilians-Universitat Wurzburg


Biochemistry, Virology