NDLI: Quasispecies diversity determines pathogenesis through cooperative interactions within a viral population

Content Provider	PubMed Central
Author	Marco, Vignuzzi Stone, Jeffrey K. Arnold, Jamie J. Cameron, Craig E. Andino, Raul
Abstract	An RNA virus population does not consist of a single genotype; rather, it is an ensemble of related sequences, named quasispecies 1–4. Quasispecies arise from rapid genomic evolution powered by the high mutation rate of RNA viral replication 5–8. While a high mutation rate is dangerous for a virus as it results in nonviable individuals, it has been hypothesized that high mutation rates create a “cloud” of potentially beneficial mutations at the population level, which afford the viral quasispecies a greater probability to evolve and adapt to new environments and challenges during infection 4,9–11. Importantly, mathematical modelling predicts that the viral quasispecies is not simply a collection of diverse mutants but a group of interactive variants, which together contribute to the characteristics of the population 4,12. In this view, viral populations, rather than individuals, are the target of evolutionary selection 4,12. To test this hypothesis we examined whether limiting genomic diversity affects viral pathogenesis. We find that poliovirus carrying a high fidelity polymerase replicates at wildtype levels but generates less genomic diversity and is unable to adapt to adverse growth conditions. In infected animals, the reduced viral diversity led to loss of neurotropism and an attenuated pathogenic phenotype. Strikingly, expanding quasispecies diversity of the high fidelity virus by chemical mutagenesis prior to infection restored neurotropism and pathogenesis. Analysis of viruses isolated from brain provides direct evidence for complementation between members within the quasispecies, indicating that selection indeed occurred at the population level rather than on individual mutants. Our study provides direct evidence for a fundamental prediction of the quasispecies theory and establishes a compelling link between mutation rate, population dynamics and pathogenesis.
Related Links	http://dx.doi.org/10.1038/nature04388
Ending Page	348
Page Count	5
Starting Page	344
File Format	PDF
ISSN	00280836
e-ISSN	14764687
Journal	Nature
Issue Number	7074
Volume Number	439
Language	English
Publisher Date	2006-02-01
Access Restriction	Open
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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