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Cell Host & Microbe: Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice

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  • Cell Host & Microbe: Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice

    Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice

    G?raldine Engels11
    , Alexandra Maximiliane Hierweger11
    , Julia Hoffmann11
    , Ren? Thieme11
    , Swantje Thiele
    , Stephanie Bertram
    , Carola Dreier
    , Patricia Resa-Infante
    , Henning Jacobsen
    , Kristin Thiele
    , Malik Alawi
    , Daniela Indenbirken
    , Adam Grundhoff
    , Svenja Siebels
    , Nicole Fischer
    , Violeta Stojanovska
    , Dami?n Muzzio
    , Federico Jensen
    , Khalil Karimi
    , Hans-Willi Mittr?cker
    , Petra Clara Arck12,Correspondence information about the author Petra Clara ArckEmail the author Petra Clara Arck
    , G?lsah Gabriel12,13,Correspondence information about the author G?lsah GabrielEmail the author G?lsah Gabriel
    11Co-first author
    12Co-senior author
    13Lead Contact


    DOI: http://dx.doi.org/10.1016/j.chom.2017.02.020 |





    Highlights

    • ?Pregnancy-associated influenza susceptibility can be mimicked in pregnant mice
    • ?Allogenically pregnant mice show a more severe infection than do syngenically mated mice
    • ?CD8+ T cell migration into the lung is impaired in allogenically pregnant infected mice
    • ?H1N1 virus variants emerge in pregnant mice that are more virulent in non-pregnant mice



    Summary

    Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8+ T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. These insights underscore the importance of influenza vaccination compliance in pregnant women and may open novel therapeutic avenues.





  • #2
    Viral infection
    The mother of all viruses


    Nature Reviews Immunology 17, 216?217 (2017) doi:10.1038/nri.2017.30 Published online 27 March 2017 Article tools



    Pregnant women are particularly vulnerable to influenza virus infection during pandemics; although this is thought to be due to suppression of the maternal immune system during pregnancy, the mechanisms involved are poorly defined. Engels et al. now report that pregnant mice develop weaker antiviral immune responses in the lungs than?


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