Fatal outcome of pandemic H1N1 2009 influenza virus infection is associated with immunopathology and impaired lung repair, not enhanced viral burden, in pregnant mice

Glendie Marcelin, Jerry R. Aldridge, Susu Duan, Hazem E. Ghoneim, Jerold Rehg, Henju Marjuki, Adrianus C M Boon, Jonathan Mccullers, Richard J. Webby

Research output: Contribution to journalArticle

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Abstract

Pandemic A (H1N1) 2009 influenza virus (pH1N1) infection in pregnant women can be severe. The mechanisms that affect infection outcome in this population are not well understood. To address this, pregnant and nonpregnant BALB/c mice were inoculated with the wild-type pH1N1 strain A/California/04/09. To determine whether innate immune responses are associated with severe infection, we measured the innate cells trafficking into the lungs of pregnant versus nonpregnant animals. Increased infiltration of pulmonary neutrophils and macrophages strongly correlated with an elevated mortality in pregnant mice. In agreement with this, the product of nitric oxide (nitrite) and several cytokines associated with recruitment and/or function of these cells were increased in the lungs of pregnant animals. Surprisingly, increased mortality in pregnant mice was not associated with higher virus load because equivalent virus titers and immunohistochemical staining were observed in the nasal cavities or lungs of all mice. To determine whether exacerbated inflammatory responses and elevated cellularity resulted in lung injury, epithelial regeneration was measured. The lungs of pregnant mice exhibited reduced epithelial regeneration, suggesting impaired lung repair. Despite these immunologic alterations, pregnant animals demonstrated equivalent percentages of pulmonary influenza virus-specific CD8 + T lymphocytes, although they displayed elevated levels of T-regulator lymphocytes (Tregs) in the lung. Also, pregnant mice mounted equal antibody titers in response to virus or immunization with a monovalent inactivated pH1N1 A/California/07/09 vaccine. Therefore, immunopathology likely caused by elevated cellular recruitment is an implicated mechanism of severe pH1N1 infection in pregnant mice.

Original languageEnglish (US)
Pages (from-to)11208-11219
Number of pages12
JournalJournal of Virology
Volume85
Issue number21
DOIs
StatePublished - Nov 1 2011

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immunopathology
Fatal Outcome
Pandemics
pandemic
Virus Diseases
Orthomyxoviridae
viral load
Viral Load
lungs
Lung
mice
infection
Regeneration
Infection
Viruses
Neutrophil Infiltration
Mortality
Nasal Cavity
Alveolar Macrophages
Lung Injury

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

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Fatal outcome of pandemic H1N1 2009 influenza virus infection is associated with immunopathology and impaired lung repair, not enhanced viral burden, in pregnant mice. / Marcelin, Glendie; Aldridge, Jerry R.; Duan, Susu; Ghoneim, Hazem E.; Rehg, Jerold; Marjuki, Henju; Boon, Adrianus C M; Mccullers, Jonathan; Webby, Richard J.

In: Journal of Virology, Vol. 85, No. 21, 01.11.2011, p. 11208-11219.

Research output: Contribution to journalArticle

Marcelin, Glendie ; Aldridge, Jerry R. ; Duan, Susu ; Ghoneim, Hazem E. ; Rehg, Jerold ; Marjuki, Henju ; Boon, Adrianus C M ; Mccullers, Jonathan ; Webby, Richard J. / Fatal outcome of pandemic H1N1 2009 influenza virus infection is associated with immunopathology and impaired lung repair, not enhanced viral burden, in pregnant mice. In: Journal of Virology. 2011 ; Vol. 85, No. 21. pp. 11208-11219.
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