Wild type and mutant 2009 pandemic influenza A (H1N1) viruses cause more severe disease and higher mortality in pregnant BALB/c mice.
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.
Kwok-Hung
KH
Chan
Anna J X
AJ
Zhang
Kelvin K W
KK
To
Chris C S
CC
Chan
Vincent K M
VK
Poon
Kunyuan
K
Guo
Fai
F
Ng
Qi-Wei
QW
Zhang
Virtual H C
VH
Leung
Annie N Y
AN
Cheung
Candy C Y
CC
Lau
Patrick C Y
PC
Woo
Herman
H
Tse
Wailan
W
Wu
Honglin
H
Chen
Bo-Jian
BJ
Zheng
Kwok-Yung
KY
Yuen
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000401:mortality / Q000503:physiopathology* / Q000821:virology; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
D000914:Antibodies, Viral; D018925:Chemokines; D016207:Cytokines