1887

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Volume 99, Issue 9

Replicase-mediated shielding of the poliovirus replicative double-stranded RNA to avoid recognition by MDA5 Free

Abstract

Replication of the positive-strand RNA viruses generates double-stranded RNAs (dsRNAs) that are recognized by host pattern recognition receptors (PRRs) to trigger innate immune responses. Formation of the viral replication complex (RC) has been thought to shield dsRNA from being recognized by innate sensors. To elucidate the RC-mediated evasion of innate recognition, we selected poliovirus (PV) as a model. We first found that RNAs generated during PV replication were potent interferon (IFN) inducers upon transfection, while there was no obvious IFN production detected in PV-replicating cells. PV replication did not interfere with IFN production when IFN agonists were synchronously introduced with the replicating PV RNAs, and in PV-infected cells, IFN agonist-induced IFN production was only moderately impaired but not completely abolished. When PV-infected cells were in situ permeabilized by digitonin, viral dsRNAs were readily detected by an anti-dsRNA antibody and were resistant to RNase III digestion. When digitonin-permeabilized cells were further solubilized by 1 % triton X-100, the dsRNAs of PV became sensitive to RNase III digestion. A co-localization study showed that PV dsRNA did not co-localize with MDA5 in virally infected cells. Given that the PV replication complex is protruding single-membrane and tubular in form, viral replicative dsRNAs are probably shielded by the replication complex or the viral replicase to avoid being accessed by RNase III and MDA5. We propose that the replication complex- or replicase-mediated shielding of dsRNA may act as a means for innate evasion.

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Keyword(s): Innate immunity , interferon , MDA5 , poliovirus , replicase and replication complex
© 2018 The Authors
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2018-07-24
2024-04-19
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Replicase-mediated shielding of the poliovirus replicative double-stranded RNA to avoid recognition by MDA5
J. Gen. Virol. 99, 1199 (2018); https://doi.org/10.1099/jgv.0.001111
/content/journal/jgv/10.1099/jgv.0.001111
/content/journal/jgv/10.1099/jgv.0.001111
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