Differential pulmonary transcriptomic profiles in murine lungs infected with low and highly virulent influenza H3N2 viruses reveal dysregulation of TREM1 signaling, cytokines, and chemokines.
Funct Integr Genomics
; 12(1): 105-17, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-21874528
ABSTRACT
Investigating the relationships between critical influenza viral mutations contributing to increased virulence and host expression factors will shed light on the process of severe pathogenesis from the systems biology perspective. We previously generated a mouse-adapted, highly virulent influenza (HVI) virus through serial lung-to-lung passaging of a human influenza H3N2 virus strain that causes low virulent influenza (LVI) in murine lungs. This HVI virus is characterized by enhanced replication kinetics, severe lung injury, and systemic spread to major organs. Our gene microarray investigations compared the host transcriptomic responses of murine lungs to LVI virus and its HVI descendant at 12, 48, and 96 h following infection. More intense expression of genes associated with cytokine activity, type 1 interferon response, and apoptosis was evident in HVI at all time-points. We highlighted dysregulation of the TREM1 signaling pathway (an amplifier of cytokine production) that is likely to be upregulated in infiltrating neutrophils in HVI-infected lungs. The cytokine gene expression changes were corroborated by elevated levels of multiple cytokine and chemokine proteins in the bronchoalveolar lavage fluid of infected mice, especially at 12 h post-infection. Concomitantly, the downregulation of genes that mediate proliferative, developmental, and metabolic processes likely contributed to the lethality of HVI as well as lack of lung repair. Overall, our comparative transcriptomic study provided insights into key host factors that influence the dynamics, pathogenesis, and outcome of severe influenza.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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Receptores Imunológicos
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Citocinas
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Infecções por Orthomyxoviridae
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Vírus da Influenza A Subtipo H3N2
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Transcriptoma
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Pulmão
Limite:
Animals
Idioma:
En
Revista:
Funct Integr Genomics
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Singapura