Hennig, Thomas and Prusty, Archana B. and Kaufer, Benedikt B. and Whisnant, Adam W. and Lodha, Manivel and Enders, Antje and Thomas, Julius and Kasimir, Francesca and Grothey, Arnhild and Klein, Teresa and Herb, Stefanie and Juerges, Christopher and Sauer, Markus and Fischer, Utz and Rudel, Thomas and Meister, Gunter and Erhard, Florian and Dölken, Lars and Prusty, Bhupesh K. (2022) Selective inhibition of miRNA processing by a herpesvirus-encoded miRNA. NATURE, 605 (7910). pp. 539-544. ISSN 0028-0836, 1476-4687
Full text not available from this repository. (Request a copy)Abstract
Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation(1,2). A long appreciated, yet undefined relationship exists between the lytic-latent switch and viral non-coding RNAs3,4. Here we identify viral microRNA (miRNA)-mediated inhibition of host miRNA processing as a cellular mechanism that human herpesvirus 6A (HHV-6A) exploits to disrupt mitochondrial architecture, evade intrinsic host defences and drive the switch from latent to lytic virus infection. We demonstrate that virus-encoded miR-aU14 selectively inhibits the processing of multiple miR-30 family members by direct interaction with the respective primary (pri)-miRNA hairpin loops. Subsequent loss of miR-30 and activation of the miR-30-p53-DRP1 axis triggers a profound disruption of mitochondrial architecture. This impairs induction of type I interferons and is necessary for both productive infection and virus reactivation. Ectopic expression of miR-aU14 triggered virus reactivation from latency, identifying viral miR-aU14 as a readily druggable master regulator of the herpesvirus lytic-latent switch. Our results show that miRNA-mediated inhibition of miRNA processing represents a generalized cellular mechanism that can be exploited to selectively target individual members of miRNA families. We anticipate that targeting miR-aU14 will provide new therapeutic options for preventing herpesvirus reactivations in HHV-6-associated disorders.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VIRUS; RNA; GENE; BIOGENESIS; PROTEIN; LET-7; CELL; IDENTIFICATION; RECOGNITION; INFECTION |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Feb 2024 10:50 |
| Last Modified: | 16 Feb 2024 10:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58115 |
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