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Published on: January 7, 2019
Preliminary microRNA analysis in lung tissue to identify potential therapeutic targets against H5N1 infection
James V Rogers1, Jennifer A Price, Morgan Q S Wendling
1Battelle, Columbus, Ohio, USA. rogersjv@battelle.org
Abstract:
Within the past decade, human infections with the highly pathogenic avian influenza H5N1 have resulted in approximately 60% mortality and increased the need for vaccines and therapeutics. Understanding the molecular events associated with pathology can aid this effort; therefore, this study was conducted to assess microRNA (miRNA) expression in mouse lungs infected with H5N1 A/Vietnam/1203/04. Intranasal administration of 1500 median tissue culture infectious dose of H5N1 promoted differences in the number and expression pattern of miRNA from lung tissue collected at 2, 4, 6, 24, and 96 h post-exposure that mapped to common biological functions. Informatics analysis identified miRNA-specific predicted genes known to be therapeutic drug targets in which Furin was common to all time periods. This study provides insight into the differential miRNA expression with respect to the host-pathogen relationship and identification of potential therapeutic drug targets.
Insights
Highly pathogenic avian influenza H5N1 infections cause high mortality. This study analyzed microRNA (miRNA) expression in mouse lungs post-H5N1 infection, identifying potential therapeutic targets like Furin.
Area of Science:
- Virology and Molecular Biology
- Immunology and Host-Pathogen Interactions
- Bioinformatics and Computational Biology
Background:
- Highly pathogenic avian influenza H5N1 poses a significant global health threat, characterized by high mortality rates in human infections.
- The urgent need for effective vaccines and therapeutics necessitates a deeper understanding of the molecular mechanisms underlying H5N1 pathogenesis.
- MicroRNAs (miRNAs) are key regulators of gene expression and play critical roles in viral infections and host immune responses.
Purpose of the Study:
- To investigate the differential expression profiles of microRNAs (miRNAs) in mouse lung tissue following H5N1 influenza virus infection.
- To identify specific miRNAs and their target genes involved in the host-pathogen interaction during H5N1 infection.
- To discover potential therapeutic drug targets based on miRNA expression patterns and predicted gene functions.
Main Methods:
- Mice were infected intranasally with a high dose (1500 median tissue culture infectious dose) of the H5N1 A/Vietnam/1203/04 strain.
- Lung tissues were collected at multiple time points post-infection (2, 4, 6, 24, and 96 hours) for analysis.
- MicroRNA (miRNA) expression profiling was performed, followed by bioinformatics analysis to predict target genes and associated biological functions.
Main Results:
- Significant alterations in the number and expression patterns of miRNAs were observed in H5N1-infected mouse lungs across different time points.
- Informatics analysis revealed that the differentially expressed miRNAs targeted genes involved in common biological functions.
- Furin was identified as a predicted target gene common to all analyzed time points, suggesting its critical role in H5N1 infection.
Conclusions:
- This study elucidates the dynamic changes in miRNA expression in response to H5N1 influenza virus infection in a mouse model.
- The findings highlight the complex host-pathogen molecular interplay mediated by miRNAs during H5N1 infection.
- The identification of specific miRNAs and their target genes, such as Furin, provides valuable insights for the development of novel therapeutic strategies against H5N1 influenza.
