Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection

Abstract A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments...

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Autores principales:	Dominik Wodarz, David N. Levy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/85fef92f686d4e41b0ec6450ad12e46d
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spelling	oai:doaj.org-article:85fef92f686d4e41b0ec6450ad12e46d2021-12-02T11:52:25ZPyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection10.1038/s41598-017-04130-92045-2322https://doaj.org/article/85fef92f686d4e41b0ec6450ad12e46d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04130-9https://doaj.org/toc/2045-2322Abstract A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus. Superinfection of latently infected cells by productive virus could similarly remove those cells through active virus replication and resulting cytopathicity. The mathematical models presented can explain a number of previously published clinical observations including latent reservoir size and the relationships to viral load in acute HIV infection, measurements of the latent reservoir in chronic infection, and the replacement of wild-type virus by CTL escape mutants within the latent reservoir. Basic virus dynamics models of latency that do not take into account pyroptosis, superinfection, or other potential complexities cannot account for the data.Dominik WodarzDavid N. LevyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dominik Wodarz David N. Levy Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection
description	Abstract A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus. Superinfection of latently infected cells by productive virus could similarly remove those cells through active virus replication and resulting cytopathicity. The mathematical models presented can explain a number of previously published clinical observations including latent reservoir size and the relationships to viral load in acute HIV infection, measurements of the latent reservoir in chronic infection, and the replacement of wild-type virus by CTL escape mutants within the latent reservoir. Basic virus dynamics models of latency that do not take into account pyroptosis, superinfection, or other potential complexities cannot account for the data.
format	article
author	Dominik Wodarz David N. Levy
author_facet	Dominik Wodarz David N. Levy
author_sort	Dominik Wodarz
title	Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection
title_short	Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection
title_full	Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection
title_fullStr	Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection
title_full_unstemmed	Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection
title_sort	pyroptosis, superinfection, and the maintenance of the latent reservoir in hiv-1 infection
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/85fef92f686d4e41b0ec6450ad12e46d
work_keys_str_mv	AT dominikwodarz pyroptosissuperinfectionandthemaintenanceofthelatentreservoirinhiv1infection AT davidnlevy pyroptosissuperinfectionandthemaintenanceofthelatentreservoirinhiv1infection
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Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection

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