Fusion and fission events regulate endosome maturation and viral escape

Abstract Endosomes are intracellular vesicles that mediate the communication of the cell with its extracellular environment. They are an essential part of the cell’s machinery regulating intracellular trafficking via the endocytic pathway. Many viruses, which in order to replicate require a host cel...

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Autores principales:	Mario Castro, Grant Lythe, Jolanda Smit, Carmen Molina-París
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/21fe7578e6cf405f9f70c13aa4de7710
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spelling	oai:doaj.org-article:21fe7578e6cf405f9f70c13aa4de77102021-12-02T18:03:21ZFusion and fission events regulate endosome maturation and viral escape10.1038/s41598-021-86877-w2045-2322https://doaj.org/article/21fe7578e6cf405f9f70c13aa4de77102021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86877-whttps://doaj.org/toc/2045-2322Abstract Endosomes are intracellular vesicles that mediate the communication of the cell with its extracellular environment. They are an essential part of the cell’s machinery regulating intracellular trafficking via the endocytic pathway. Many viruses, which in order to replicate require a host cell, attach themselves to the cellular membrane; an event which usually initiates uptake of a viral particle through the endocytic pathway. In this way viruses hijack endosomes for their journey towards intracellular sites of replication and avoid degradation without host detection by escaping the endosomal compartment. Recent experimental techniques have defined the role of endosomal maturation in the ability of enveloped viruses to release their genetic material into the cytoplasm. Endosome maturation depends on a family of small hydrolase enzymes (or GTPases) called Rab proteins, arranged on the cytoplasmic surface of its membrane. Here, we model endosomes as intracellular compartments described by two variables (its levels of active Rab5 and Rab7 proteins) and which can undergo coagulation (or fusion) and fragmentation (or fission). The key element in our approach is the “per-cell endosomal distribution” and its dynamical (Boltzmann) equation. The Boltzmann equation allows us to derive the dynamics of the total number of endosomes in a cell, as well as the mean and the standard deviation of its active Rab5 and Rab7 levels. We compare our mathematical results with experiments of Dengue viral escape from endosomes. The relationship between endosomal active Rab levels and pH suggests a mechanism that can account for the observed variability in viral escape times, which in turn regulate the viability of a viral intracellular infection.Mario CastroGrant LytheJolanda SmitCarmen Molina-ParísNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mario Castro Grant Lythe Jolanda Smit Carmen Molina-París Fusion and fission events regulate endosome maturation and viral escape
description	Abstract Endosomes are intracellular vesicles that mediate the communication of the cell with its extracellular environment. They are an essential part of the cell’s machinery regulating intracellular trafficking via the endocytic pathway. Many viruses, which in order to replicate require a host cell, attach themselves to the cellular membrane; an event which usually initiates uptake of a viral particle through the endocytic pathway. In this way viruses hijack endosomes for their journey towards intracellular sites of replication and avoid degradation without host detection by escaping the endosomal compartment. Recent experimental techniques have defined the role of endosomal maturation in the ability of enveloped viruses to release their genetic material into the cytoplasm. Endosome maturation depends on a family of small hydrolase enzymes (or GTPases) called Rab proteins, arranged on the cytoplasmic surface of its membrane. Here, we model endosomes as intracellular compartments described by two variables (its levels of active Rab5 and Rab7 proteins) and which can undergo coagulation (or fusion) and fragmentation (or fission). The key element in our approach is the “per-cell endosomal distribution” and its dynamical (Boltzmann) equation. The Boltzmann equation allows us to derive the dynamics of the total number of endosomes in a cell, as well as the mean and the standard deviation of its active Rab5 and Rab7 levels. We compare our mathematical results with experiments of Dengue viral escape from endosomes. The relationship between endosomal active Rab levels and pH suggests a mechanism that can account for the observed variability in viral escape times, which in turn regulate the viability of a viral intracellular infection.
format	article
author	Mario Castro Grant Lythe Jolanda Smit Carmen Molina-París
author_facet	Mario Castro Grant Lythe Jolanda Smit Carmen Molina-París
author_sort	Mario Castro
title	Fusion and fission events regulate endosome maturation and viral escape
title_short	Fusion and fission events regulate endosome maturation and viral escape
title_full	Fusion and fission events regulate endosome maturation and viral escape
title_fullStr	Fusion and fission events regulate endosome maturation and viral escape
title_full_unstemmed	Fusion and fission events regulate endosome maturation and viral escape
title_sort	fusion and fission events regulate endosome maturation and viral escape
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/21fe7578e6cf405f9f70c13aa4de7710
work_keys_str_mv	AT mariocastro fusionandfissioneventsregulateendosomematurationandviralescape AT grantlythe fusionandfissioneventsregulateendosomematurationandviralescape AT jolandasmit fusionandfissioneventsregulateendosomematurationandviralescape AT carmenmolinaparis fusionandfissioneventsregulateendosomematurationandviralescape
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Fusion and fission events regulate endosome maturation and viral escape

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