A molecular mechanism for probabilistic bet hedging and its role in viral latency

Sonali Chaturvedi, Jonathan Klein, Noam Vardi, Cynthia Bolovan-Fritts, Marie Wolf, Kelvin Du, Luwanika Mlera, Meredith Calvert, Nathaniel J. Moorman, Felicia Goodrum, Bo Huang, Leor S. Weinberger

Research output: Contribution to journalArticle

Abstract

Probabilistic bet hedging, a strategy to maximize fitness in unpredictable environments by matching phenotypic variability to environmental variability, is theorized to account for the evolution of various fate-specification decisions, including viral latency. However, the molecular mechanisms underlying bet hedging remain unclear. Here, we report that large variability in protein abundance within individual herpesvirus virion particles enables probabilistic bet hedging between viral replication and latency. Superresolution imaging of individual virions of the human herpesvirus cytomegalovirus (CMV) showed that virion-to-virion levels of pp71 tegument protein-the major viral transactivator protein-exhibit extreme variability. This super-Poissonian tegument variability promoted alternate replicative strategies: high virion pp71 levels enhance viral replicative fitness but, strikingly, impede silencing, whereas low virion pp71 levels reduce fitness but promote silencing. Overall, the results indicate that stochastic tegument packaging provides a mechanism enabling probabilistic bet hedging between viral replication and latency.

Original languageEnglish (US)
Pages (from-to)17240-17248
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number29
DOIs
StatePublished - Jul 21 2020

Keywords

  • Fate selection
  • Herpesvirus
  • Latency
  • Stochastic variability
  • Tegument

ASJC Scopus subject areas

  • General

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  • Cite this

    Chaturvedi, S., Klein, J., Vardi, N., Bolovan-Fritts, C., Wolf, M., Du, K., Mlera, L., Calvert, M., Moorman, N. J., Goodrum, F., Huang, B., & Weinberger, L. S. (2020). A molecular mechanism for probabilistic bet hedging and its role in viral latency. Proceedings of the National Academy of Sciences of the United States of America, 117(29), 17240-17248. https://doi.org/10.1073/pnas.1914430117