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Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study


Gene expression profiling of human blood cells might uncover the complex dynamics of host response to ARIs such as pandemic H1N1. However, only limited data are available on the system level response to naturally acquired infections. To understand the molecular bases and network orchestration of host responses, we prospectively enrolled 1610 healthy adults in the fall of 2009 and 2010, followed the subjects with influenza-like illness (N = 133) for 3 weeks, and examined changes in their peripheral blood gene expression. We discovered distinct phases of the host response spanning 6 days after infection, and identified genes that differentiate influenza from non-influenza virus infection. We then moved the focus from gene expression patterns to gene co-expression patterns. We detected gene modules that are related to core features of regulatory networks and found a substantial increase in the connectivity of the influenza responsive genes. Finally, we identified a molecular signature that correlated significantly with antibody response to pH1N1 virus. Taken together, our findings offer insights into the molecular mechanisms underlying host response to influenza virus infection, and provide a valuable foundation for investigation of the global coordinated responses to ARIs. Molecular correlates of the immune response suggest targets for intervention and improved vaccines.


Vyšlo v časopise: Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004869
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004869

Souhrn

Gene expression profiling of human blood cells might uncover the complex dynamics of host response to ARIs such as pandemic H1N1. However, only limited data are available on the system level response to naturally acquired infections. To understand the molecular bases and network orchestration of host responses, we prospectively enrolled 1610 healthy adults in the fall of 2009 and 2010, followed the subjects with influenza-like illness (N = 133) for 3 weeks, and examined changes in their peripheral blood gene expression. We discovered distinct phases of the host response spanning 6 days after infection, and identified genes that differentiate influenza from non-influenza virus infection. We then moved the focus from gene expression patterns to gene co-expression patterns. We detected gene modules that are related to core features of regulatory networks and found a substantial increase in the connectivity of the influenza responsive genes. Finally, we identified a molecular signature that correlated significantly with antibody response to pH1N1 virus. Taken together, our findings offer insights into the molecular mechanisms underlying host response to influenza virus infection, and provide a valuable foundation for investigation of the global coordinated responses to ARIs. Molecular correlates of the immune response suggest targets for intervention and improved vaccines.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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