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

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 under...

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Autores principales: Chaturvedi, Sonali, Klein, Jonathan, Vardi, Noam, Bolovan-Fritts, Cynthia, Wolf, Marie, Du, Kelvin, Mlera, Luwanika, Calvert, Meredith, Moorman, Nathaniel J., Goodrum, Felicia, Huang, Bo, Weinberger, Leor S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382263/
https://www.ncbi.nlm.nih.gov/pubmed/32632017
http://dx.doi.org/10.1073/pnas.1914430117
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author Chaturvedi, Sonali
Klein, Jonathan
Vardi, Noam
Bolovan-Fritts, Cynthia
Wolf, Marie
Du, Kelvin
Mlera, Luwanika
Calvert, Meredith
Moorman, Nathaniel J.
Goodrum, Felicia
Huang, Bo
Weinberger, Leor S.
author_facet Chaturvedi, Sonali
Klein, Jonathan
Vardi, Noam
Bolovan-Fritts, Cynthia
Wolf, Marie
Du, Kelvin
Mlera, Luwanika
Calvert, Meredith
Moorman, Nathaniel J.
Goodrum, Felicia
Huang, Bo
Weinberger, Leor S.
author_sort Chaturvedi, Sonali
collection PubMed
description 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.
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spelling pubmed-73822632020-07-30 A molecular mechanism for probabilistic bet hedging and its role in viral latency Chaturvedi, Sonali Klein, Jonathan Vardi, Noam Bolovan-Fritts, Cynthia Wolf, Marie Du, Kelvin Mlera, Luwanika Calvert, Meredith Moorman, Nathaniel J. Goodrum, Felicia Huang, Bo Weinberger, Leor S. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2020-07-21 2020-07-06 /pmc/articles/PMC7382263/ /pubmed/32632017 http://dx.doi.org/10.1073/pnas.1914430117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Chaturvedi, Sonali
Klein, Jonathan
Vardi, Noam
Bolovan-Fritts, Cynthia
Wolf, Marie
Du, Kelvin
Mlera, Luwanika
Calvert, Meredith
Moorman, Nathaniel J.
Goodrum, Felicia
Huang, Bo
Weinberger, Leor S.
A molecular mechanism for probabilistic bet hedging and its role in viral latency
title A molecular mechanism for probabilistic bet hedging and its role in viral latency
title_full A molecular mechanism for probabilistic bet hedging and its role in viral latency
title_fullStr A molecular mechanism for probabilistic bet hedging and its role in viral latency
title_full_unstemmed A molecular mechanism for probabilistic bet hedging and its role in viral latency
title_short A molecular mechanism for probabilistic bet hedging and its role in viral latency
title_sort molecular mechanism for probabilistic bet hedging and its role in viral latency
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382263/
https://www.ncbi.nlm.nih.gov/pubmed/32632017
http://dx.doi.org/10.1073/pnas.1914430117
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