TITLE

Wild Type and Mutant 2009 Pandemic Influenza A (H1N1) Viruses Cause More Severe Disease and Higher Mortality in Pregnant BALB/c Mice

AUTHOR(S)

Kwok-Hung Chan; Zhang, Anna J. X.; To, Kelvin K. W.; Chan, Chris C. S.; Poon, Vincent K. M.; Kunyuan Guo; Fai Ng; Qi-Wei Zhang; Leung, Virtual H. C.; Cheung, Annie N. Y.; Lau, Candy C. Y.; Woo, Patrick C. Y.; Herman Tse; Wailan Wu; Honglin Chen; Bo-Jian Zheng; Kwok-Yung Yuen

PUB. DATE

October 2010

SOURCE

PLoS ONE;2010, Vol. 5 Issue 10, p1

SOURCE TYPE

Academic Journal

DOC. TYPE

Article

ABSTRACT

Background: Pregnant women infected by the pandemic influenza A (H1N1) 2009 virus had more severe disease and higher mortality but its pathogenesis is still unclear. Principal Findings: 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. Conclusion: 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.

ACCESSION #

59308763

Tags: H1N1 (2009) influenza;  PANDEMICS;  MUTATION (Biology);  CELL lines;  HEMAGGLUTININ;  CYTOKINES;  GENETIC markers;  PREGNANCY -- Complications;  REVERSE transcriptase polymerase chain reaction

 

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