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Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation

Hepatitis C (HCV), hepatitis B (HBV), the human immunodeficiency viruses (HIV), and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide. These viruses circulate within infected hosts as vast populations of closely related, but geneti...

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Detalles Bibliográficos
Autor principal: Sallie, Richard
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC552327/
https://www.ncbi.nlm.nih.gov/pubmed/15707489
http://dx.doi.org/10.1186/1743-422X-2-10
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author Sallie, Richard
author_facet Sallie, Richard
author_sort Sallie, Richard
collection PubMed
description Hepatitis C (HCV), hepatitis B (HBV), the human immunodeficiency viruses (HIV), and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide. These viruses circulate within infected hosts as vast populations of closely related, but genetically diverse, molecules known as "quasispecies". The mechanism(s) by which this extreme genetic and antigenic diversity is stably maintained are unclear, but are fundamental to understanding viral persistence and pathobiology. The persistence of HCV, an RNA virus, is especially problematic and HCV stability, maintained despite rapid genomic mutation, is highly paradoxical. This paper presents the hypothesis, and evidence, that viruses capable of persistent infection autoregulate replication and the likely mechanism mediating autoregulation – Replicative Homeostasis – is described. Replicative homeostasis causes formation of stable, but highly reactive, equilibria that drive quasispecies expansion and generates escape mutation. Replicative homeostasis explains both viral kinetics and the enigma of RNA quasispecies stability and provides a rational, mechanistic basis for all observed viral behaviours and host responses. More importantly, this paradigm has specific therapeutic implication and defines, precisely, new approaches to antiviral therapy. Replicative homeostasis may also modulate cellular gene expression.
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spelling pubmed-5523272005-03-06 Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation Sallie, Richard Virol J Hypothesis Hepatitis C (HCV), hepatitis B (HBV), the human immunodeficiency viruses (HIV), and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide. These viruses circulate within infected hosts as vast populations of closely related, but genetically diverse, molecules known as "quasispecies". The mechanism(s) by which this extreme genetic and antigenic diversity is stably maintained are unclear, but are fundamental to understanding viral persistence and pathobiology. The persistence of HCV, an RNA virus, is especially problematic and HCV stability, maintained despite rapid genomic mutation, is highly paradoxical. This paper presents the hypothesis, and evidence, that viruses capable of persistent infection autoregulate replication and the likely mechanism mediating autoregulation – Replicative Homeostasis – is described. Replicative homeostasis causes formation of stable, but highly reactive, equilibria that drive quasispecies expansion and generates escape mutation. Replicative homeostasis explains both viral kinetics and the enigma of RNA quasispecies stability and provides a rational, mechanistic basis for all observed viral behaviours and host responses. More importantly, this paradigm has specific therapeutic implication and defines, precisely, new approaches to antiviral therapy. Replicative homeostasis may also modulate cellular gene expression. BioMed Central 2005-02-11 /pmc/articles/PMC552327/ /pubmed/15707489 http://dx.doi.org/10.1186/1743-422X-2-10 Text en Copyright © 2005 Sallie; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Hypothesis
Sallie, Richard
Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation
title Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation
title_full Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation
title_fullStr Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation
title_full_unstemmed Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation
title_short Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation
title_sort replicative homeostasis: a fundamental mechanism mediating selective viral replication and escape mutation
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC552327/
https://www.ncbi.nlm.nih.gov/pubmed/15707489
http://dx.doi.org/10.1186/1743-422X-2-10
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