Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease

The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2016-12, Vol.354 (6316), p.1148-1152
Main Authors: Akiyama, Benjamin M., Laurence, Hannah M., Massey, Aaron R., Costantino, David A., Xie, Xuping, Yang, Yujiao, Shi, Pei-Yong, Nix, Jay C., Beckham, J. David, Kieft, Jeffrey S.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
BASIC BIOLOGICAL SCIENCES
Cellular structure
Chlorocebus aethiops
Crystal structure
Culicidae - virology
Disorders
Epithelial Cells - virology
Exoribonucleases - chemistry
Exoribonucleases - genetics
Flaviviridae
Flavivirus
Humans
In vitro testing
Mice
Molecular biology
Molecular structure
Monkeys
Mutation
Neurons - virology
Nucleic Acid Conformation
Ribonucleic acid
Ribonucleic acids
RNA
RNA, Untranslated - chemistry
RNA, Untranslated - genetics
RNA, Viral - chemistry
RNA, Viral - genetics
Vero Cells
Viruses
Zika virus
Zika Virus - genetics
Zika Virus - metabolism
Zika Virus Infection - virology
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Summary:The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonudease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonudease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonudease resistance and identifies features that may modulate function in diverse flaviviruses.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aah3963