Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596557
Title: Investigation of the antiviral properties of Mx proteins
Author: Benfield, C. T. C.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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Abstract:
Cell culture and in vitro assays were employed to investigate the antiviral activity of Asn631 chicken Mix alleles. Infection of primary chick embryo fibroblast cultures with influenza (A/WSN/33) revealed that the Asn631 genotype had no impact on multicycle replication. The Shamo (SHK) chicken Mx allele (Asn631) was reconstructed using mutagenesis because this was the only allele previously reported to inhibit influenza virus. However, SHK Mx did not inhibit influenza gene expression or influenza minireplicon systems in transfected 293T cells. artificial nuclear localisation did not confer anti-orthomyxovirus activity on chicken Mx. Chicken Mx also lacked activity against a Thogoto minireplicon or Newcastle disease virus gene expression. thus, selective breeding to enhance the frequency of Asn631 chicken Mx alleles in chicken populations is not warranted. The assays employed here could provide efficient screens to test for antiviral activity of other chicken Mx alleles. Cell background (chicken vs. human) differentially influenced the ability of human MxA and murine Mx1 to inhibit a minireplicon system based on an avian (A/Turkey/50-92/91) strain of influenza. The mutations PB2 E627K, PB2 D701N, PB2 S714R and NP N319K enhanced avian influenza polymerase activity in human cells, but did not reduce the sensitivity of reconstituted influenza vRNPs to MxA or Mx1. In stably transfected 3T3 cells, human MxA induced cytoplasmic aggregates of the influenza (A/WSN/33) nucleoprotein but did not perturb the normal subcellular localisation of influenza mRNA. These data support the hypothesis that MxA inhibits influenza replication by sequestering nascent NP within the cytoplasma, and preventing its nuclear import. Finally, an inhibitory effect of human MxA against Newcastle Disease Virus (NDV) was identified. Preliminary data indicated that MxA differentially inhibits the expression of different NDV genes, and that NDV replication induces the relocalisation of MxA into cytoplasmic inclusions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.596557  DOI: Not available
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