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

GÉRALDINE ENGELS; RENÉ THIEME; CAROLA DREIER; KRISTIN THIELE; DAMIAN MUZZIO; HANS-WILLI MITTRUCKER; ALEXANDRA MAXIMILIANE HIERWEGER; SWANTJE THIELE; PATRICIA RESA-INFANTE; MALIK ALAWI; FEDERICO JENSEN; PETRA CLARA ARCK; JULIA HOFFMANN; STEPHANIE BERTRAM; HENNING JACOBSEN; DANIELA INDENBIRKEN; KHALIL KARIM; GULSAH GABRIEL

CELL HOST & MICROBE

CELL PRESS

Lugar: United States; Año: 2017 vol. 21

1931-3128

Pregnant women are at high risk for severe influenzadisease outcomes, yet insights into the underlyingmechanisms are limited. Here, we present models ofH1N1 infection in syngenic and allogenic pregnantmice; infection in the latter mirrors the severe courseof 2009 pandemic influenza in pregnant women. Wefound that the anti-viral immune response in the pregnanthost was significantly restricted as compared tothe non-pregnant host. This included a reduced type Iinterferon response as well as impaired migration ofCD8+ T cells into the lung. The multi-faceted failureto mount an anti-viral response in allogenic pregnantmice resulted in a less stringent selective environmentthat promoted the emergence of 2009 H1N1 virusvariants that specifically counteract type I interferonresponse and mediate increased viral pathogenicity.These insights underscore the importance of influenzavaccination compliance in pregnant womenand may open novel therapeutic avenues.