Machine Learning Identifies Cellular and Exosomal MicroRNA Signatures of Lyssavirus Infection in Human Stem Cell-Derived Neurons

Frontiers in Cellular and Infection Microbiology

Carmel M. O’Brien¹  Vinod Sundaramoorthy²  Nathan Godde²  John Bingham²  Diane Green²  Ryan J. Farr²  Megan Dearnley²  Cameron Stewart³  Christopher Cowled³ 

[1] Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia;Commonwealth Scientific and Industrial Research Organisation (CSIRO) Australian Animal Health Laboratory at the Australian Centre for Disease Preparedness, Geelong, VIC, Australia;Commonwealth Scientific and Industrial Research Organisation (CSIRO) Health and Biosecurity at the Australian Centre for Disease Preparedness, Geelong, VIC, Australia;Commonwealth Scientific and Industrial Research Organisation (CSIRO) Manufacturing, Clayton, VIC, Australia;

关键词: microRNA;    lyssavirus;    stem cells;    neural;    neurons;    biomarker;   

DOI  :  10.3389/fcimb.2021.783140

来源: DOAJ

【 摘 要 】

Despite being vaccine preventable, rabies (lyssavirus) still has a significant impact on global mortality, disproportionally affecting children under 15 years of age. This neurotropic virus is deft at avoiding the immune system while travelling through neurons to the brain. Until recently, research efforts into the role of non-coding RNAs in rabies pathogenicity and detection have been hampered by a lack of human in vitro neuronal models. Here, we utilized our previously described human stem cell-derived neural model to investigate the effect of lyssavirus infection on microRNA (miRNA) expression in human neural cells and their secreted exosomes. Conventional differential expression analysis identified 25 cellular and 16 exosomal miRNAs that were significantly altered (FDR adjusted P-value <0.05) in response to different lyssavirus strains. Supervised machine learning algorithms determined 6 cellular miRNAs (miR-99b-5p, miR-346, miR-5701, miR-138-2-3p, miR-651-5p, and miR-7977) were indicative of lyssavirus infection (100% accuracy), with the first four miRNAs having previously established roles in neuronal function, or panic and impulsivity-related behaviors. Another 4-miRNA signatures in exosomes (miR-25-3p, miR-26b-5p, miR-218-5p, miR-598-3p) can independently predict lyssavirus infected cells with >99% accuracy. Identification of these robust lyssavirus miRNA signatures offers further insight into neural lineage responses to infection and provides a foundation for utilizing exosome miRNAs in the development of next-generation molecular diagnostics for rabies.

【 授权许可】

Unknown