Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.
PLoS One. 2010 Oct 29;5(10):e13757. doi: 10.1371/journal.pone.0013757.
Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear.
We showed that higher mortality, more severe pneumonitis, higher pulmonary viral load, lower peripheral blood T lymphocytes and antibody responses, higher levels of proinflammatory cytokines and chemokines, and worse fetal development occurred in pregnant mice than non-pregnant controls infected by either wild type (clinical isolate) or mouse-adapted mutant virus with D222G substitution in hemagglutinin. These disease-associated changes and the lower respiratory tract involvement were worse in pregnant mice challenged by mutant virus. Though human placental origin JEG-3 cell line could be infected and proinflammatory cytokines or chemokines were elevated in amniotic fluid of some mice, no placental or fetal involvement by virus were detected by culture, real-time reverse transcription polymerase chain reaction or histopathological changes. Dual immunofluorescent staining of viral nucleoprotein and type II alveolar cell marker SP-C protein suggested that the majority of infected alveolar epithelial cells were type II pneumocytes.
The adverse effect of this pandemic virus on maternal and fetal outcome is largely related to the severe pulmonary disease and the indirect effect of inflammatory cytokine spillover into the systemic circulation.
感染大流行流感 A（H1N1）2009 病毒的孕妇疾病更严重，死亡率更高，但发病机制尚不清楚。
我们发现，与未感染的对照组相比，感染野生型（临床分离株）或血凝素中具有 D222G 取代的小鼠适应性突变病毒的怀孕小鼠死亡率更高、更严重的肺炎、更高的肺部病毒载量、外周血 T 淋巴细胞和抗体反应更低、促炎细胞因子和趋化因子水平更高，以及胎儿发育更差。在怀孕小鼠中用突变病毒进行挑战时，这些与疾病相关的变化和下呼吸道受累情况更严重。尽管人胎盘来源的 JEG-3 细胞系可以被感染，并且一些小鼠的羊水内细胞因子或趋化因子水平升高，但通过培养、实时逆转录聚合酶链反应或组织病理学变化均未检测到病毒对胎盘或胎儿的影响。病毒核蛋白和 II 型肺泡细胞标记物 SP-C 蛋白的双重免疫荧光染色表明，大多数感染的肺泡上皮细胞为 II 型肺泡细胞。
这种大流行病毒对母婴结局的不利影响主要与严重的肺部疾病以及炎症细胞因子溢出到全身循环的间接影响有关。
