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February 3, 2017PLoS PathogensOpen Access

EndoU-deficient coronaviruses are severely attenuated in vivo and in primary cells due to early induction of double-stranded RNA host cell responses, including IFN-I expression and RNase L activation.

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Population

Preclinical models including C57BL/6 mice, various knockout mice, murine L929 fibroblasts, primary murine…

Comparison

Infection with EndoU-deficient coronaviruses vs Infection with wild-type coronaviruses or mock…

Design

Preclinical

Key result

EndoU-deficient coronaviruses are severely attenuated in vivo and in primary cells due to early induction of double-stranded RNA host cell responses, including IFN-I expression and RNase L activation.

Authors

EKEveline KindlerCGCristina Gil‐CruzJSJulia Spanier

Discussion

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Overview

May guide antiviral targeting of EndoU; hypothesis-generating from animal models only.

Structured PICO

P
Population
In vitro and in vivo mouse models investigating the role of coronavirus endonuclease (EndoU) in innate immune evasion.
I
Intervention
Infection with EndoU-deficient coronaviruses (MHVH277A and HCoV-229EH250A)
C
Comparator
Infection with wild-type coronaviruses (MHV-A59 and HCoV-229E) or mock infection
O
Outcome
Viral replication (titers in pfu and viral RNA copies) and host innate immune response activation (IFN-β expression, rRNA integrity/RNase L activation, eIF2α phosphorylation/PKR activation)surrogate

Coronavirus endonuclease (EndoU) activity is a critical evolutionary conserved mechanism that allows the virus to evade early host innate immune responses by preventing the simultaneous activation of dsRNA sensors like Mda5, OAS, and PKR.

Cite This Study

Kindler et al. (2017) studied Coronavirus infection. EndoU-deficient coronaviruses vs. Wild-type coronaviruses was evaluated on Viral replication and innate immune response. EndoU-deficient coronaviruses are severely attenuated in vivo and in primary cells due to early induction of double-stranded RNA host cell responses, including IFN-I expression and RNase L activation.

synapsesocial.com/papers/6a346ea3824a1c938b52761chttps://doi.org/10.1371/journal.ppat.1006195
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