title: 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 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.
authors.affiliation: Research Group Viral Zoonosis and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany; Department of Obstetrics and Fetal Medicine, Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Engels
authors.affiliation: Department of Obstetrics and Fetal Medicine, Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Institute for Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Alexandra Maximiliane
authors.initials: AM
authors.lastname: Hierweger
authors.affiliation: Research Group Viral Zoonosis and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoffmann
authors.affiliation: Department of Obstetrics and Fetal Medicine, Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Thieme
authors.affiliation: Research Group Viral Zoonosis and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Thiele
authors.affiliation: Research Group Viral Zoonosis and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bertram
authors.affiliation: Research Group Viral Zoonosis and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Dreier
authors.affiliation: Research Group Viral Zoonosis and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Resa-Infante
authors.affiliation: Research Group Viral Zoonosis and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Jacobsen
authors.affiliation: Department of Obstetrics and Fetal Medicine, Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Thiele
authors.affiliation: Research Group Viral Genomics, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Malik
authors.initials: M
authors.lastname: Alawi
authors.affiliation: Research Group Viral Genomics, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Indenbirken
authors.affiliation: Research Group Viral Genomics, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors.forename: Adam
authors.initials: A
authors.lastname: Grundhoff
authors.affiliation: Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Siebels
authors.affiliation: Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Fischer
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center, 9713 Groningen, NL.
authors.forename: Violeta
authors.initials: V
authors.lastname: Stojanovska
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, 17475 Greifswald, Germany.
authors.forename: Damián
authors.initials: D
authors.lastname: Muzzio
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, 17475 Greifswald, Germany; Laboratory for Immunology of Pregnancy, Center for Pharmacological and Botanical Studies (CEFYBO-CONICET), School of Medicine, University of Buenos Aires, 1053 Buenos Aires, Argentina.
authors.forename: Federico
authors.initials: F
authors.lastname: Jensen
authors.affiliation: Institute for Hepatology and Experimental Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Khalil
authors.initials: K
authors.lastname: Karimi
authors.affiliation: Institute for Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.affiliation: Department of Obstetrics and Fetal Medicine, Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. Electronic address: p.arck@uke.de.
authors.forename: Petra Clara
authors.initials: PC
authors.lastname: Arck
authors.affiliation: Research Group Viral Zoonosis and Adaptation, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany; Centre for Structural and Cell Biology in Medicine, University of Lübeck, 23562 Lübeck, Germany. Electronic address: guelsah.gabriel@hpi.uni-hamburg.de.
authors.forename: Gülsah
authors.initials: G
authors.lastname: Gabriel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000821:virology*; D012641:Selection, Genetic; D014774:Virulence
keywords: NS1 R211K mutation; allogenic mating; influenza; leukocyte homing; mice; pandemic; pregnancy; progesterone; type I response; viral quasi species