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.
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.
Cell Host Microbe. 2017 Mar 8;21(3):321-333. doi: 10.1016/j.chom.2017.02.020.
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.
孕妇患严重流感的风险很高，但对其潜在机制的了解有限。在这里，我们建立了同基因和异基因感染的怀孕小鼠模型；后者模拟了 2009 年大流行期间孕妇的严重流感病程。我们发现，与非怀孕宿主相比，怀孕宿主的抗病毒免疫反应受到严重限制。这包括Ⅰ型干扰素反应减少以及 CD8 T 细胞向肺部迁移受损。异基因怀孕小鼠中这种多方面的抗病毒反应失败导致选择环境不严格，从而促进了 2009 年 H1N1 病毒变异株的出现，这些变异株专门拮抗Ⅰ型干扰素反应并介导病毒毒力增加。这些研究结果强调了孕妇流感疫苗接种的重要性，并可能开辟新的治疗途径。
