Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.

Efforts to reduce the viral load of human immunodeficiency virus type 1 (HIV-1) during long-term treatment are challenged by the evolution of anti-viral resistance mutants. Recent studies have shown that gene therapy approaches based on conditionally replicating vectors (CRVs) could have many advant...

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Autores principales:	Ruian Ke, James O Lloyd-Smith
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8a34b565a0fb4c28b7d77b569d94daaa
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spelling	oai:doaj.org-article:8a34b565a0fb4c28b7d77b569d94daaa2021-11-18T05:52:45ZEvolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.1553-734X1553-735810.1371/journal.pcbi.1002744https://doaj.org/article/8a34b565a0fb4c28b7d77b569d94daaa2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133349/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Efforts to reduce the viral load of human immunodeficiency virus type 1 (HIV-1) during long-term treatment are challenged by the evolution of anti-viral resistance mutants. Recent studies have shown that gene therapy approaches based on conditionally replicating vectors (CRVs) could have many advantages over anti-viral drugs and other approaches to therapy, potentially including the ability to circumvent the problem of evolved resistance. However, research to date has not explored the evolutionary consequences of long-term treatment of HIV-1 infections with conditionally replicating vectors. In this study, we analyze a computational model of the within-host co-evolutionary dynamics of HIV-1 and conditionally replicating vectors, using the recently proposed 'therapeutic interfering particle' as an example. The model keeps track of the stochastic process of viral mutation, and the deterministic population dynamics of T cells as well as different strains of CRV and HIV-1 particles. We show that early in the co-infection, mutant HIV-1 genotypes that escape suppression by CRV therapy appear; this is similar to the dynamics observed in drug treatments and other gene therapies. In contrast to other treatments, however, the CRV population is able to evolve and catch up with the dominant HIV-1 escape mutant and persist long-term in most cases. On evolutionary grounds, gene therapies based on CRVs appear to be a promising tool for long-term treatment of HIV-1. Our model allows us to propose design principles to optimize the efficacy of this class of gene therapies. In addition, because of the analogy between CRVs and naturally-occurring defective interfering particles, our results also shed light on the co-evolutionary dynamics of wild-type viruses and their defective interfering particles during natural infections.Ruian KeJames O Lloyd-SmithPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 10, p e1002744 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Ruian Ke James O Lloyd-Smith Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.
description	Efforts to reduce the viral load of human immunodeficiency virus type 1 (HIV-1) during long-term treatment are challenged by the evolution of anti-viral resistance mutants. Recent studies have shown that gene therapy approaches based on conditionally replicating vectors (CRVs) could have many advantages over anti-viral drugs and other approaches to therapy, potentially including the ability to circumvent the problem of evolved resistance. However, research to date has not explored the evolutionary consequences of long-term treatment of HIV-1 infections with conditionally replicating vectors. In this study, we analyze a computational model of the within-host co-evolutionary dynamics of HIV-1 and conditionally replicating vectors, using the recently proposed 'therapeutic interfering particle' as an example. The model keeps track of the stochastic process of viral mutation, and the deterministic population dynamics of T cells as well as different strains of CRV and HIV-1 particles. We show that early in the co-infection, mutant HIV-1 genotypes that escape suppression by CRV therapy appear; this is similar to the dynamics observed in drug treatments and other gene therapies. In contrast to other treatments, however, the CRV population is able to evolve and catch up with the dominant HIV-1 escape mutant and persist long-term in most cases. On evolutionary grounds, gene therapies based on CRVs appear to be a promising tool for long-term treatment of HIV-1. Our model allows us to propose design principles to optimize the efficacy of this class of gene therapies. In addition, because of the analogy between CRVs and naturally-occurring defective interfering particles, our results also shed light on the co-evolutionary dynamics of wild-type viruses and their defective interfering particles during natural infections.
format	article
author	Ruian Ke James O Lloyd-Smith
author_facet	Ruian Ke James O Lloyd-Smith
author_sort	Ruian Ke
title	Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.
title_short	Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.
title_full	Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.
title_fullStr	Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.
title_full_unstemmed	Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.
title_sort	evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8a34b565a0fb4c28b7d77b569d94daaa
work_keys_str_mv	AT ruianke evolutionaryanalysisofhumanimmunodeficiencyvirustype1therapiesbasedonconditionallyreplicatingvectors AT jamesolloydsmith evolutionaryanalysisofhumanimmunodeficiencyvirustype1therapiesbasedonconditionallyreplicatingvectors
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Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.

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