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Reference: Gaunt, E, Wise, HM, Zhang, H et al., (2016). Elevation of CpG frequencies in influenza A genome attenuates pathogenicity but enhances host response to infection. eLife, 5.Citable link to this page:

 

Elevation of CpG frequencies in influenza A genome attenuates pathogenicity but enhances host response to infection.

Abstract: Previously, we demonstrated that frequencies of CpG and UpA dinucleotides profoundly influence the replication ability of echovirus 7 (Tulloch et al., 2014). Here, we show that that influenza A virus (IAV) with maximised frequencies of these dinucleotides in segment 5 showed comparable attenuation in cell culture compared to unmodified virus and a permuted control (CDLR). Attenuation was also manifested in vivo, with 10-100 fold reduced viral loads in lungs of mice infected with 200PFU of CpG-high and UpA-high mutants. However, both induced powerful inflammatory cytokine and adaptive (T cell and neutralising antibody) responses disproportionate to their replication. CpG-high infected mice also showed markedly reduced clinical severity, minimal weight loss and reduced immmunopathology in lung, yet sterilising immunity to lethal dose WT challenge was achieved after low dose (20PFU) pre-immunisation with this mutant. Increasing CpG dinucleotide frequencies represents a generic and potentially highly effective method for generating safe, highly immunoreactive vaccines.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's versionNotes:Copyright Gaunt et al. This article is distributed under the terms of the Creative Commons Attribution License. This is the publisher's version of the article. The final version is available online from eLife Sciences Publications at: [10.7554/eLife.12735]

Bibliographic Details

Publisher: eLife Sciences Publications

Publisher Website: http://elife.elifesciences.org/

Journal: eLifesee more from them

Publication Website: http://www.elifesciences.org/

Issue Date: 2016-02-16Identifiers

Urn: uuid:67c18144-2b62-4c23-b18e-374e1ba4b704

Source identifier: 605951

Eissn: 2050-084X

Doi: https://doi.org/10.7554/elife.12735 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: infectious disease microbiology viruses Tiny URL: pubs:605951

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Author: Gaunt, E - - - Wise, HM - - - Zhang, H - - - Lee, LN - institutionUniversity of Oxford Oxford, MSD, NDM grantNumberWT091663MA fun

Source: https://ora.ox.ac.uk/objects/uuid:67c18144-2b62-4c23-b18e-374e1ba4b704



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