What question did this study set out to answer?

To determine whether a specific threonine residue at position 538 of the nonstructural protein nsP1 mediates adult mouse neurovirulence in the Sindbis-group alphavirus S.A.AR86.

May 1, 2000Journal of VirologyOpen Access

A Single Amino Acid Change in nsP1 Attenuates Neurovirulence of the Sindbis-Group Alphavirus S.A.AR86

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Authors

MHMark T. HeiseUniversity of North Carolina at Chapel Hill DSDennis A. SimpsonUniversity of North Carolina at Chapel Hill RJRobert E. JohnstonRutgers, The State University of New Jersey

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Implication

Experimental study reveals that mutating nsP1 position 538 attenuates alphavirus neurovirulence in adult mice, highlighting a key nonstructural protein role in viral encephalitis.

Key Points

To determine whether a specific threonine residue at position 538 of the nonstructural protein nsP1 mediates adult mouse neurovirulence in the Sindbis-group alphavirus S.A.AR86.
Generated mutant clone ps51 by substituting isoleucine for threonine at nsP1 position 538 in the neurovirulent S.A.AR86 clone (ps55), and introduced threonine at position 538 into the nonneurovirulent Sindbis virus TR339 (39ns1).
Evaluated viral replication kinetics in cell culture and determined morbidity, mortality, and viral titers following intracranial inoculation in mice.
Tracked spatial and temporal viral replication within infected mouse brains between 12 and 72 hours postinfection using in situ hybridization.
Intracranial infection with wild-type s55 caused hind limb paresis, conjunctivitis, weight loss, and 89% mortality in mice, whereas the mutant s51 induced milder clinical signs and 0% mortality despite reaching equivalent brain viral titers.
In situ hybridization showed wild-type s55 disseminated widely across brain tissue at late time points postinfection, while the attenuated s51 mutant remained spatially restricted.
Introducing Thr-538 into nonneurovirulent Sindbis strain TR339 significantly increased neurovirulence, causing substantial weight loss and hind limb paresis.

Cite This Study

Heise et al. (2000) studied this question.

synapsesocial.com/papers/6aa4ce0cf188d5f0710a4b96 https://doi.org/10.1128/jvi.74.9.4207-4213.2000

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Implication

Experimental study reveals that mutating nsP1 position 538 attenuates alphavirus neurovirulence in adult mice, highlighting a key nonstructural protein role in viral encephalitis.

A Single Amino Acid Change in nsP1 Attenuates Neurovirulence of the Sindbis-Group Alphavirus S.A.AR86

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Implication

Key Points

Cite This Study

A Single Amino Acid Change in nsP1 Attenuates Neurovirulence of the Sindbis-Group Alphavirus S.A.AR86

Discussion

Member takes

Implication

Key Points

Cite This Study

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