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November 20, 2024Comparative MedicineOpen Access

While EV-D68 lethality was completely penetrant in wild-type and heterozygous mice, all AGB6-Setd3-/- littermates survived, indicating SETD3 is essential for EV-D68 pathogenesis.

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Why the study?

No approved antiviral compounds or vaccines exist for EV-D68, and an appropriate mouse model is needed to develop therapeutics.

Population

AGB6, AB6, GB6, parental B6, and AGB6-Setd3 mice

Comparison

EV-D68 infection across strains and Setd3 genotypes

Design

Preclinical animal model study

Key result

While EV-D68 lethality was completely penetrant in wild-type and heterozygous mice, all AGB6-Setd3-/- littermates survived, indicating SETD3 is essential for EV-D68 pathogenesis.

Authors

TWTanya WatarastapornWSWenqi SongJGJeffrey S. Glenn

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Overview

AG129 mice support preclinical EV-D68 antiviral screening; leaves open translation to human AFM therapies.

Structured PICO

P
Population
Mouse models including AGB6 (double knockout of Ifnar1 and Ifngr1 on C57BL/6 background), AB6, GB6, B6 strains, and AGB6 mice with Setd3 knockout alleles, infected with EV-D68.
I
Intervention
Setd3 gene knockout (AGB6-Setd3-/-)
C
Comparator
Wild-type and heterozygous littermates (AGB6-Setd3+/+ and AGB6-Setd3+/-)
O
Outcome
Survival/lethality following EV-D68 infectionhard clinical

Main Result

Absolute Event Rate: 100% vs 0%

SETD3 is essential for EV-D68 pathogenesis in a novel AGB6 mouse model, highlighting it as a promising therapeutic target for enterovirus infections.

Cite This Study

Watarastaporn et al. (2024) studied EV-D68 acute flaccid myelitis (mouse model). Setd3 knockout (AGB6-Setd3-/- mice) vs. AGB6-Setd3+/+ and AGB6-Setd3+/- mice was evaluated on Survival / EV-D68 lethality. While EV-D68 lethality was completely penetrant in wild-type and heterozygous mice, all AGB6-Setd3-/- littermates survived, indicating SETD3 is essential for EV-D68 pathogenesis.

synapsesocial.com/papers/6a63c3ceaab374d588f2d5b2https://doi.org/10.30802/aalas-cm-24-058
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