H5N1 virus causes significant perturbations in host proteome very early in influenza virus-infected primary human
Chung Yan Cheung1, Eric Y Chan, Alexei Krasnoselsky
1Centre of Influenza Research & School of Public Health, University of Hong Kong.
Abstract:
H5N1 influenza viruses, which cause disease in humans, have unusually high pathogenicity. The temporal response of primary human monocyte-derived macrophages infected with highly pathogenic H5N1 and seasonal H1N1 influenza viruses was evaluated using mass spectrometry-based quantitative proteomic profiling. This was done in order to demonstrate significant perturbation of the host proteome upon viral infection, as early as 1 hour after infection. This early host response distinguished H5N1 infection from H1N1 infection, the latter inducing less of a response. The most pronounced effect was observed on the translational machinery, suggesting that H5N1 might gain advantage in replication by using the cell protein synthesis machinery early in the infection.
Insights
Highly pathogenic H5N1 influenza virus infection significantly alters host cell proteomes early on, distinguishing it from H1N1. H5N1 targets the translational machinery for replication advantage.
Area of Science:
- Virology
- Immunology
- Proteomics
Background:
- Highly pathogenic H5N1 influenza viruses cause severe human disease.
- Understanding the host response to influenza infection is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the temporal host proteome response in human macrophages infected with H5N1 and H1N1 influenza viruses.
- To identify early host response markers distinguishing H5N1 from H1N1 infection.
Main Methods:
- Primary human monocyte-derived macrophages were infected with H5N1 and H1N1 influenza viruses.
- Quantitative proteomic profiling using mass spectrometry was employed to analyze host protein changes.
- Temporal analysis was performed as early as 1 hour post-infection.
Main Results:
- Significant perturbation of the host proteome was observed as early as 1 hour after infection.
- The early host response differed significantly between H5N1 and H1N1 infections, with H5N1 inducing a more pronounced response.
- The translational machinery was the most affected cellular component, suggesting its exploitation by H5N1.
Conclusions:
- Early host proteome profiling can distinguish H5N1 from H1N1 influenza virus infections.
- H5N1 influenza virus may gain a replication advantage by targeting the host's translational machinery early in infection.
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