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

Muhammad Atif Zahoor,Sophia Osawe,Xiao-Dan Yao,Kenneth L Rosenthal,Alash’Le Abimiku,Bethany M Henrick,Chris P Verschoor

doi:10.1038/s41598-020-69799-x

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.

Highlights

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
Most of the infants born to HIV-1 positive women do not become infected themselves, which is potentially attributed to the anti-HIV-1 molecules present in human milk (HM)[5,6]
We investigated the expression profile of HIV-1 associated miRNAs in Human milk (HM) samples collected from HIV-1 infected women and identified a total of 19 miRNAs which were differentially expressed in women infected with HIV-1 and targeted the cellular genes that are involved in multiple biological pathways including cell cycle, pathways in cancer, viral carcinogenesis, adherens junctions, TGF-β signaling, fatty acid biosynthesis, p53 signaling and apoptosis

Summary

Introduction

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. The receiver operating characteristics (ROC) curve analyses of miR-630 and miR378g 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 motherto-child transmission (MTCT) of HIV-1. An intervention that promotes exclusive breastfeeding, regardless of HIV status of the mother shows decreased vertical HIV transmission rates compared to infants who are non-exclusively breastfed[1,3] The mechanisms underlying this phenomenon remain unknown; data presented here may provide new insights into potential preventative and therapeutic strategies that may be useful for both infants and adults in the future[4]. Exosomes are nanosized intraluminal extracellular vesicles secreted by a variety of cells that are present in almost all biological fluids

Methods

Results

Conclusion