RGD Reference Report - In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein. - Rat Genome Database

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In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein.

Authors: Deeg, Christoph M  Hassan, Ebrahim  Mutz, Pascal  Rheinemann, Lara  Götz, Veronika  Magar, Linda  Schilling, Mirjam  Kallfass, Carsten  Nürnberger, Cindy  Soubies, Sébastien  Kochs, Georg  Haller, Otto  Schwemmle, Martin  Staeheli, Peter 
Citation: Deeg CM, etal., J Exp Med. 2017 May 1;214(5):1239-1248. doi: 10.1084/jem.20161033. Epub 2017 Apr 10.
RGD ID: 126777675
Pubmed: PMID:28396461   (View Abstract at PubMed)
PMCID: PMC5413327   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.20161033   (Journal Full-text)

Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses. Here, we describe a new mouse model suitable for such risk assessment, based on the observation that the innate restriction factor MxA represents an effective species barrier that must be overcome by zoonotic viruses. Our mouse lacks functional endogenous Mx genes but instead carries the human MX1 locus as a transgene. Such transgenic mice were largely resistant to highly pathogenic avian H5 and H7 influenza A viruses, but were almost as susceptible to infection with influenza viruses of human origin as nontransgenic littermates. Influenza A viruses that successfully established stable lineages in humans have acquired adaptive mutations which allow partial MxA escape. Accordingly, an engineered avian H7N7 influenza virus carrying a nucleoprotein with signature mutations typically found in human virus isolates was more virulent in transgenic mice than parental virus, demonstrating that a few amino acid changes in the viral target protein can mediate escape from MxA restriction in vivo. Similar mutations probably need to be acquired by emerging influenza A viruses before they can spread in the human population.



Disease Annotations    Click to see Annotation Detail View
RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MX1Humanavian influenza susceptibilityIMP human gene in a mouse modelRGD 
Mx1Ratavian influenza susceptibilityISOMX1 (Homo sapiens)human gene in a mouse modelRGD 
Mx1Mouseavian influenza susceptibilityISOMX1 (Homo sapiens)human gene in a mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mx1  (MX dynamin like GTPase 1)

Genes (Mus musculus)
Mx1  (MX dynamin-like GTPase 1)

Genes (Homo sapiens)
MX1  (MX dynamin like GTPase 1)


Additional Information