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

Abstract

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.