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bioRxiv · 10.1101/322651

Protein mismatches caused by reassortment influence functions of the reovirus capsid

Thete, D.·Danthi, P.
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Abstract

Following attachment to host receptors via {sigma}1, reovirus particles are endocytosed and disassembled to generate infectious subvirion particles (ISVPs). ISVPs undergo conformational changes to form ISVP*, releasing {sigma}1 and membrane-targeting peptides from the viral 1 protein. ISVP* formation is required for delivery of the viral core into the cytoplasm for replication. We characterized the properties of T3DF/T3DCS1, a S1 gene monoreassortant between two laboratory isolates of prototype reovirus strain T3D: T3DF and T3DC. T3DF/T3DCS1 is poorly infectious. This deficiency is a consequence of inefficient encapsidation of S1-encoded {sigma}1 on T3DF/T3DCS1 virions. Additionally, in comparison to T3DF, T3DF/T3DCS1 undergoes ISVP-to-ISVP* conversion more readily, revealing an unexpected role for {sigma}1 in regulating ISVP* formation. The {sigma}1 protein is held within turrets formed by the {lambda}2 protein. To test if the altered properties of T3DF/T3DCS1 are due to a mismatch between {sigma}1 and {lambda}2 proteins from T3DF and T3DC, properties of T3DF/T3DCL2 and T3DF/T3DCS1L2, which express a T3DC-derived {lambda}2, were compared. The presence of T3DC {lambda}2 allowed more efficient {sigma}1 incorporation, producing particles that exhibit T3DF-like infectivity. In comparison to T3DF, T3DF/T3DCL2 prematurely converts to ISVP* uncovering a role for {lambda}2 in regulating ISVP* formation. Importantly, a virus with matching {sigma}1 and {lambda}2 displayed a more regulated conversion to ISVP* than either T3DF/T3DCS1 or T3DF/T3DCL2. In addition to identifying new regulators of ISVP* formation, our results highlight that protein mismatches produced by reassortment can alter virus assembly and thereby influence subsequent functions of the virus capsid.

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Thete, D., Danthi, P.. 2018-05-15. Protein mismatches caused by reassortment influence functions of the reovirus capsid. https://doi.org/10.1101/322651

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