Combinatorial Effects of miRNAs in HSV-2 Infection of Macrophages: An In Silico and In Vitro Integration Approach
Author:
Banerjee Anwesha1, Dass Debashree1, Dhotre Kishore1ORCID, Wakchoure Pooja2, More Ashwini1, Rana Santanu3ORCID, Khan Abdul A.2, Mukherjee Anupam1ORCID
Affiliation:
1. Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, MH, India 2. Division of Microbiology, ICMR-National AIDS Research Institute, Pune 411026, MH, India 3. Department of Zoology, RPMC-University of Calcutta, Uttarpara 712258, WB, India
Abstract
The rising issues of herpes simplex virus (HSV)-2 drug ramifications have encouraged the researchers to look for new and alternative approaches that pose minimum adversities in the host while efficiently reducing the HSV-2 infection. Although microRNAs (miRNAs), as unorthodox approaches, are gaining popularity due to eliciting highly reduced immunogenic reactions, their implications in HSV-2 research have been rarely explored. In this study, a pool of cellular miRNAs with significance in HSV-2-induced inflammatory and immune responses have been identified. Computationally recognizing the host targets of these miRNAs through network biology and machine learning, in vitro validation has been addressed along with the identification of their regulation in the HSV-2 infection. To signify the role of these identified miRNAs, they have been individually ectopically expressed in macrophages. The ectopic expression of the individual miRNAs was able to suppress HSV-2 viral gene expression. Taking a step forward, this study also highlights the Box–Behnken design-based combinatorial effect of ectopically expressed miRNAs on maximum suppression of HSV-2 infectivity. Therefore, the concentrations of each of the miRNAs optimized in a combination, predicted through expert systems biology tools were validated in vitro to not only recover the target expressions but also inhibit the HSV-2 infection in the macrophages. Overall, the study offers miRNAs as intriguing alternatives to commercially available medications against HSV-2. Moreover, the study illuminates the prophylactic potentiality of the miRNAs, which is significant since there are currently no vaccines available for HSV-2. Moving forward, the miRNAs are employed in an innovative strategy that incorporates intricate biological system models and in vitro confirmation methods to deliver a prospective combinatorial miRNA therapeutic against HSV-2 infection.
Funder
Department of Science and Technology, Science and Engineering Research Board (DST-SERB), Government of India Department of Health Research (DHR) Young Scientist Grant ICMR-National AIDS Research Institute, Pune, India Indian Council of Medical Research
Subject
Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology
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