Expression profiling of human milk derived exosomal microRNAs and their targets in HIV‐1 infected mothers

Authors

Muhammad Atif Zahoor, McMaster University, Hamilton & Toronto Center for Liver Disease, Toronto General Hospital Research Institute (TGHRI)Follow
McMaster University, Hamilton, McMaster University, Hamilton
Bethany M. Henrick, Evolve Biosystems Inc. & University of Nebraska- LincolnFollow
Chris P. Verschoor, McMaster University, Hamilton
Alash’le Abimiku, Institue of Human Virology-Nigeria & University of Maryland
Sophia Osawe, Institue of Human Virology-Nigeria
Kenneth L. Rosenthal, McMaster UniversityFollow

Document Type

Article

Date of this Version

2020

Citation

Scientific Reports | (2020) 10:12931 | https://doi.org/10.1038/s41598-020-69799-x

Comments

The Author(s) 2020

Abstract

Despite the use of antiretroviral therapy (ART) in HIV‐1 infected mothers approximately 5% of new HIV‐1 infections still occur in breastfed infants annually, which warrants for the development of novel strategies to prevent new HIV‐1 infections in infants. Human milk (HM) exosomes are highly enriched in microRNAs (miRNAs), which play an important role in neonatal immunity. Furthermore, HM exosomes from healthy donors are known to inhibit HIV‐1 infection and transmission; however, the effect of HIV‐1 on HM exosomal miRNA signatures remains unknown. In this study, we used nCounter NanoString technology and investigated miRNAs expression profiles in first week postpartum HM exosomes from HIV‐1 infected and uninfected control mothers (n = 36). Our results indicated that HIV‐1 perturbed the differential expression patterns of 19 miRNAs (13 upregulated and 6 downregulated) in HIV‐1 infected women compared to healthy controls. DIANA‐miR functional pathway analyses revealed that multiple biological pathways are involved including cell cycle, pathways in cancer, TGF‐β signaling, FoxO signaling, fatty acid biosynthesis, p53 signaling and apoptosis. Moreover, the receiver operating characteristics (ROC) curve analyses of miR‐630 and miR‐ 378g yielded areas under the ROC curves of 0.82 (95% CI 0.67 to 0.82) and 0.83 (95% CI 0.67 to 0.83), respectively highlighting their potential to serve as biomarkers to identify HIV‐1 infection in women. These data may contribute to the development of new therapeutic strategies in prevention of mother‐ to‐child transmission (MTCT) of HIV‐1.