Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 428904
Title Mutations in the M-Gene Segment Can Substantially Increase Replication Efficiency of NS1 Deletion Influenza A Virus in MDCK Cells
Author(s) Wielink, R. van; Harmsen, M.M.; Martens, D.E.; Peeters, B.P.H.; Wijffels, R.H.; Moormann, R.J.M.
Source Journal of Virology 86 (2012)22. - ISSN 0022-538X - p. 12341 - 12350.
Department(s) Bioprocess Engineering
CVI Virology
Publication type Refereed Article in a scientific journal
Publication year 2012
Keyword(s) interferon antagonist ns1 - messenger-rnas - infected-cells - protein expression - apoptosis - vaccine - translation - activation - domain - vero
Abstract Influenza viruses unable to express NS1 protein (delNS1) replicate poorly and induce high amounts of interferon (IFN). They are therefore considered as candidate viruses for live-attenuated influenza vaccines. Their attenuated replication is generally assumed to result from the inability to counter the antiviral host response, as delNS1 viruses replicate efficiently in Vero cells, which lack IFN expression. In this study, delNS1 virus was parallel passaged on IFN competent MDCK cells, which resulted in two strains that were able to replicate to high virus titres in MDCK cells due to adaptive mutations in especially the M-gene segment, but also the NP and NS gene segments. Most notable were clustered U-to-C mutations in the M segment of both strains and clustered A-to-G mutations in the NS segment of one strain, which presumably resulted from host cell mediated RNA editing. The M segment mutations in both strains changed the ratio of M1 to M2 expression, probably by affecting splicing efficiency. In one virus, 2 amino acid substitutions in M1 additionally enhanced virus replication, possibly through changes in the M1 distribution between the nucleus and the cytoplasm. Both adapted viruses induced equal levels of IFN as delNS1 virus. These results show that the increased replication of the adapted viruses is not primarily due to altered IFN induction, but rather related to changes in M1 expression or localization. The mutations identified in this paper may be used to enhance delNS1 virus replication for vaccine production.
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