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bioRxiv · 10.1101/2022.11.10.515810

The reovirus σ1 attachment protein influences the stability of its entry intermediate

Garcia, M.·Danthi, P.
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Abstract

Structural metastability of viral capsids is pivotal for viruses to survive in harsh environments and to undergo timely conformational changes required for cell entry. Mammalian orthoreovirus (reovirus) is a model to study capsid metastability. Following initial disassembly of the reovirus particle mediated by proteases, a metastable intermediate called the infectious subvirion particle (ISVP) is generated. Using a {sigma}1 monoreassortant virus, we recently showed that {sigma}1 properties affect its encapsidation on particles and the metastability of ISVPs. How metastability is impacted by {sigma}1 and whether the lower encapsidation level of {sigma}1 is connected to this property is unknown. To define a correlation between encapsidation of {sigma}1 and ISVP stability, we generated mutant viruses with single amino acid polymorphisms in {sigma}1 or those that contain chimeric {sigma}1 molecules composed of {sigma}1 portions from Type 1 and Type 3 reovirus strains. We found that under most conditions where {sigma}1 encapsidation on the particle was lower, ISVPs displayed lower stability. By separating wild-type particles based on the level of encapsidated {sigma}1, we also found that lower {sigma}1 encapsidation leads to lower ISVP stability. Characterization of mutant viruses selected for enhanced stability via a forward genetic approach also revealed that in some cases, {sigma}1 properties influence stability without influencing {sigma}1 encapsidation. These data indicate that {sigma}1 can also influence ISVP stability independent of its level of incorporation. Together, our work reveals an underappreciated effect of the {sigma}1 attachment protein on the properties of the reovirus capsid.

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Garcia, M., Danthi, P.. 2022-11-11. The reovirus σ1 attachment protein influences the stability of its entry intermediate. https://doi.org/10.1101/2022.11.10.515810

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