A study of the virulence in mice of high copying fidelity variants of human enterovirus 71
| Autor: | Peter C. McMinn, Sara Sadeghipour |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
DNA Mutational Analysis Mutation Missense Virulence Biology medicine.disease_cause Article Virus Mice Virology Enterovirus Infections medicine Animals Missense mutation Myositis Polymerase Survival analysis Mice Inbred BALB C Mutation Animal Structures RNA-Dependent RNA Polymerase medicine.disease Survival Analysis Phenotype Enterovirus A Human Disease Models Animal Infectious Diseases Amino Acid Substitution biology.protein Mutant Proteins |
| Zdroj: | Virus Research |
| ISSN: | 0168-1702 |
| Popis: | Highlights • Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of HEV71. • Mouse-adapted HEV71 strains were constructed to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus. • S264L and S264L-G64R were attenuated compared to G64R and parental virus. • Parental virus and G64R infection induced severe generalised necrotising myositis. • S264L and S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis. Polioviruses with a G64S mutation in the 3D polymerase have enhanced replication fidelity and are attenuated in animal models. Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of human enterovirus 71 (HEV71), with mutations at positions 3D-S264L, 3D-G64R or at 3D-S264L plus 3D-G64R. Mouse-adapted strains (MP-G64R, MP-S264L and MP-S264L-G64R) were constructed in order to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus (MP-26M). MP-S264L and MP-S264L-G64R were attenuated in mice (mean survival time 7.0 and 7.5 days p.i., respectively) compared to MP-G64R and MP-26M (mean survival time 6.5 and 6.0 days p.i., respectively). MP-26M and MP-G64R infection induced early onset, severe generalised necrotising myositis, whereas MP-S264L and MP-S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis. Our findings demonstrate that only the 3D-S264L mutation attenuates HEV71 in mice, suggesting that the high replication fidelity phenotype is not essential for virulence attenuation in this model. |
| Databáze: | OpenAIRE |
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