Abstract
BackgroundPregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear.Principal FindingsWe 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.ConclusionThe 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.
Highlights
The pandemic influenza A(H1N1) 2009 virus caused similar spectrum of illness as seasonal influenza virus except for more severe diseases in younger adults with little cross-reactive neutralizing antibody [1,2,3,4]
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
To understand the pathogenesis of this novel virus in pregnancy, we analyze the chemokine and cytokine profiles, viral load and histopathological changes in placental cell line and BALB/c mice infected by the wild type pandemic influenza A(H1N1) 2009 virus, which is a clinical isolate from a patient with mild disease, and a D222G mutant, which can cause severe clinical outcome
Summary
The pandemic influenza A(H1N1) 2009 virus caused similar spectrum of illness as seasonal influenza virus except for more severe diseases in younger adults with little cross-reactive neutralizing antibody [1,2,3,4]. We and others showed that the substitution of glutamate by glycine at position 222 of the viral hemagglutinin (D222G by H1 numbering or D225G by H3 numbering) was found to be significantly more frequent in patients with severe pandemic influenza H1N1 [[13,14,15,16,17,18] This mutant virus often existed as quasispecies, and had increased predilection for the lower respiratory tract [13]. To understand the pathogenesis of this novel virus in pregnancy, we analyze the chemokine and cytokine profiles, viral load and histopathological changes in placental cell line and BALB/c mice infected by the wild type pandemic influenza A(H1N1) 2009 virus, which is a clinical isolate from a patient with mild disease, and a D222G mutant, which can cause severe clinical outcome. Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear
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