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Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch

Reassortment is fundamental to the evolution of influenza viruses and plays a key role in the generation of epidemiologically significant strains. Previous studies indicate that reassortment is restricted by segment mismatch, arising from functional incompatibilities among components of two viruses....

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Autores principales: Marshall, Nicolle, Priyamvada, Lalita, Ende, Zachary, Steel, John, Lowen, Anice C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681746/
https://www.ncbi.nlm.nih.gov/pubmed/23785286
http://dx.doi.org/10.1371/journal.ppat.1003421
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author Marshall, Nicolle
Priyamvada, Lalita
Ende, Zachary
Steel, John
Lowen, Anice C.
author_facet Marshall, Nicolle
Priyamvada, Lalita
Ende, Zachary
Steel, John
Lowen, Anice C.
author_sort Marshall, Nicolle
collection PubMed
description Reassortment is fundamental to the evolution of influenza viruses and plays a key role in the generation of epidemiologically significant strains. Previous studies indicate that reassortment is restricted by segment mismatch, arising from functional incompatibilities among components of two viruses. Additional factors that dictate the efficiency of reassortment remain poorly characterized. Thus, it is unclear what conditions are favorable for reassortment and therefore under what circumstances novel influenza A viruses might arise in nature. Herein, we describe a system for studying reassortment in the absence of segment mismatch and exploit this system to determine the baseline efficiency of reassortment and the effects of infection dose and timing. Silent mutations were introduced into A/Panama/2007/99 virus such that high-resolution melt analysis could be used to differentiate all eight segments of the wild-type and the silently mutated variant virus. The use of phenotypically identical parent viruses ensured that all progeny were equally fit, allowing reassortment to be measured without selection bias. Using this system, we found that reassortment occurred efficiently (88.4%) following high multiplicity infection, suggesting the process is not appreciably limited by intracellular compartmentalization. That co-infection is the major determinant of reassortment efficiency in the absence of segment mismatch was confirmed with the observation that the proportion of viruses with reassortant genotypes increased exponentially with the proportion of cells co-infected. The number of reassortants shed from co-infected guinea pigs was likewise dependent on dose. With 10(6) PFU inocula, 46%–86% of viruses isolated from guinea pigs were reassortants. The introduction of a delay between infections also had a strong impact on reassortment and allowed definition of time windows during which super-infection led to reassortment in culture and in vivo. Overall, our results indicate that reassortment between two like influenza viruses is efficient but also strongly dependent on dose and timing of the infections.
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spelling pubmed-36817462013-06-19 Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch Marshall, Nicolle Priyamvada, Lalita Ende, Zachary Steel, John Lowen, Anice C. PLoS Pathog Research Article Reassortment is fundamental to the evolution of influenza viruses and plays a key role in the generation of epidemiologically significant strains. Previous studies indicate that reassortment is restricted by segment mismatch, arising from functional incompatibilities among components of two viruses. Additional factors that dictate the efficiency of reassortment remain poorly characterized. Thus, it is unclear what conditions are favorable for reassortment and therefore under what circumstances novel influenza A viruses might arise in nature. Herein, we describe a system for studying reassortment in the absence of segment mismatch and exploit this system to determine the baseline efficiency of reassortment and the effects of infection dose and timing. Silent mutations were introduced into A/Panama/2007/99 virus such that high-resolution melt analysis could be used to differentiate all eight segments of the wild-type and the silently mutated variant virus. The use of phenotypically identical parent viruses ensured that all progeny were equally fit, allowing reassortment to be measured without selection bias. Using this system, we found that reassortment occurred efficiently (88.4%) following high multiplicity infection, suggesting the process is not appreciably limited by intracellular compartmentalization. That co-infection is the major determinant of reassortment efficiency in the absence of segment mismatch was confirmed with the observation that the proportion of viruses with reassortant genotypes increased exponentially with the proportion of cells co-infected. The number of reassortants shed from co-infected guinea pigs was likewise dependent on dose. With 10(6) PFU inocula, 46%–86% of viruses isolated from guinea pigs were reassortants. The introduction of a delay between infections also had a strong impact on reassortment and allowed definition of time windows during which super-infection led to reassortment in culture and in vivo. Overall, our results indicate that reassortment between two like influenza viruses is efficient but also strongly dependent on dose and timing of the infections. Public Library of Science 2013-06-13 /pmc/articles/PMC3681746/ /pubmed/23785286 http://dx.doi.org/10.1371/journal.ppat.1003421 Text en © 2013 Marshall et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Marshall, Nicolle
Priyamvada, Lalita
Ende, Zachary
Steel, John
Lowen, Anice C.
Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch
title Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch
title_full Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch
title_fullStr Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch
title_full_unstemmed Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch
title_short Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch
title_sort influenza virus reassortment occurs with high frequency in the absence of segment mismatch
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681746/
https://www.ncbi.nlm.nih.gov/pubmed/23785286
http://dx.doi.org/10.1371/journal.ppat.1003421
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