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

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  • PLoS Pathogens: Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch

    Citation: Marshall N, Priyamvada L, Ende Z, Steel J, Lowen AC (2013) Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch. PLoS Pathog 9(6): e1003421. doi:10.1371/journal.ppat.1003421

    Abstract

    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 106 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.
    Author Summary

    Reassortment is the process by which influenza viruses, which carry RNA genomes comprising eight segments, exchange genetic material. Reassortment of the genome segments of two differing influenza strains has the potential to vastly increase the diversity of circulating influenza viruses. Despite its importance to influenza virus evolution, the frequency with which reassortment occurs in a cell or an animal infected with two or more variant viruses is unclear. Toward determining how readily reassortment can occur, we assessed the incidence of reassortment during experimental infection in cultured cells and in guinea pigs. We found that reassortment can occur with high efficiency in both systems, but that that efficiency is dependent on i) the dose of each virus added to the cells or taken up by the host and ii) the relative timing with which each virus infects. These results suggest that influenza A virus reassortment may be more prevalent in nature than one might expect based on the results of surveillance studies.



  • #2
    Re: PLoS Pathogens: Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch

    my summary:
    2 strains of A/Panama/2007/99, one with synonymous mutations,
    106 PFU into guinea pigs gave 46%?86% reassortants
    I'm interested in expert panflu damage estimates
    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

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