Wide Gaps in Immune Responses Post Flu Infection

Genomic signatures differentiate symptomatic, asymptomatic individuals infected with influenza A

MONDAY, Aug. 29 (HealthDay News) -- The wide gap in the antiviral and inflammatory response seen in symptomatic and asymptomatic individuals exposed to influenza A infection is mediated by genomic signatures, according to a study published online Aug. 25 in PLoS Genetics.

Yongsheng Huang, Ph.D., from the University of Michigan in Ann Arbor, and colleagues investigated the key immune response events that determine the pathogenicity of influenza A viral infection. A total of 17 healthy adults underwent nasal inoculation with live H3N2/Wisconsin influenza, and changes in host peripheral blood gene expression were examined at 16 time points over 132 hours. Distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infection were presented.

The investigators found that, based on clinically uninformed factor analysis of gene expression profiles, a specific molecular signature was associated with symptomatic disease. A total of 42 biomarkers, which differentiated between early and late phases of infection, were identified based on their expression patterns. In symptomatic hosts, there was over-stimulation of multiple viral sensing pathways, and the temporal trajectory was correlated with the development of clinical signs and symptoms. Inflammatory cytokine profiles contributed to pathogenesis with an increase preceding disease onset by 36 hours. In subclinical asymptomatic hosts, genes involved in inflammation activation and encoding virus interacting proteins were regulated transcriptionally. There was also evidence of active anti-oxidant and cell-mediated immune response.

"Our results establish a temporal pattern of host molecular responses, which differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique nonpassive response signature, suggesting novel putative molecular targets both for prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza," the authors write.

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