Identification of Critical Genes and Pathways for Influenza A Virus Infections via Bioinformatics Analysis

Abstract

Influenza A virus (IAV) requires the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only reveals molecular pathways exploited by the virus or triggered by the immune system but also provides further targets for antiviral drug development. To uncover critical pathways and potential targets of influenza infection, we assembled a large amount of data from 8 RNA sequencing studies of IAV infection for integrative network analysis. Weighted gene co-expression network analysis (WGCNA) was performed to investigate modules and genes correlated with the time course of infection and/or multiplicity of infection (MOI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and pathways of the genes in 5 significant modules. Top hub genes were identified using the cytoHubba plugin in the protein interaction network. The correlation between expression levels of 7 top hub genes and time course or MOI was displayed and validated, including BCL2L13, PLSCR1, ARID5A, LMO2, NDRG4, HAP1, and CARD10. Dysregulated expression of these genes potently impacted the development of IAV infection through modulating IAV-related biological processes and pathways. This study provides further insights into the underlying molecular mechanisms and potential targets in IAV infection.

Biological properties of the BCL-2 family protein BCL-RAMBO, which regulates apoptosis, mitochondrial fragmentation, and mitophagy

“…TaqMan arrays on apoptotic gene expression revealed that BCL-RAMBO, in addition to BCL-2-binding component 3, is expressed at higher levels in euploid embryos than in aneuploid embryos (Lal et al, 2022). A bioinformatics analysis identified BCL-RAMBO as one of the seven top hub genes down-regulated by an influenza A virus infection (Chen et al, 2022), indicating that BCL-RAMBO is involved in influenza A virus-induced mitophagy. Collectively, these findings show that BCL-RAMBO expression fluctuates to control its proapoptotic or mitophagy-inducing activity.…”

System Biology Approach to Identify the Hub Genes and Pathways Associated with Human H5N1 Infection

“…Currently, the vaccines against H5N1virus available on the market primarily target the haemagglutinin surface antigens. However, by the time a vaccine is released on the market, a new strain of haemagglutinin develops resistance [ 18 ]. Nevertheless, the systems biology approach can provide a powerful platform for identifying potential hub genes that can target surface antigens and adequately understand relative signalling pathways to develop effective vaccines [ 18 , 19 ].…”

“…However, by the time a vaccine is released on the market, a new strain of haemagglutinin develops resistance [ 18 ]. Nevertheless, the systems biology approach can provide a powerful platform for identifying potential hub genes that can target surface antigens and adequately understand relative signalling pathways to develop effective vaccines [ 18 , 19 ]. The integration of computational methods has drastically reduced the vaccine development process from 15–20 years to 2–3 years and further allows the screening of multiple novel candidates [ 17 ].…”