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June 26, 2019Socio-Environmental Systems ModelingOpen Access

The role of ZAP and OAS3/RNAseL pathways in the attenuation of an RNA virus with elevated frequencies of CpG and UpA dinucleotides

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Population

Cell lines infected with echovirus 7 mutants and replicons with elevated CpG and UpA dinucleotides

Comparison

Knockout vs reconstitution of ZAP, OAS3, RNAseL, or OAS1

Design

In vitro laboratory study

Authors

VOValerie OdonJFJelke J. FrosNGNiluka Goonawardane

Discussion

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Overview

ZAP restricts UpA-high echoviruses in vitro; leaves open dinucleotide-based attenuation strategies for vaccines.

Structured PICO

P
Population
Cell lines (including ZAP knockout, OAS3 knockout, and RNAseL knockout) infected with echovirus 7 (E7) mutants with elevated frequencies of CpG and UpA dinucleotides
I
Intervention
Knockout of ZAP, OAS3, RNAseL, or OAS1; plasmid-derived reconstitution of ZAP expression
C
Comparator
Wild-type cells or unmutated viruses
O
Outcome
Viral replication and attenuationsurrogate

The attenuation of RNA viruses with elevated CpG and UpA dinucleotides depends synergistically on ZAP and OAS3/RNAseL pathways, which has implications for the development of live attenuated vaccines against neurotropic viruses.

Cite This Study

Odon et al. (2019) studied this question.

synapsesocial.com/papers/6a9524de6a42edee3f2c9d4chttps://doi.org/10.1093/nar/gkz581
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