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Updated: Mar 23, 2026
MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Role of human GRP75 in miRNA mediated regulation of dengue virus replication
Pavan Kumar Kakumani1, Guruprasad R Medigeshi2, Inderjeet Kaur1
1International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Abstract:
In recent times, RNAi has emerged as an important defence system that regulates replication of pathogens in host cells. Many RNAi related host factors especially the host miRNAs play important roles in all intrinsic cellular functions, including viral infection. We have been working on identification of mammalian host factors involved in Dengue virus infection. In the present study, we identified Glucose Regulated Protein 75kDa (GRP75), as a host factor that is associated with dicer complex, in particular with HADHA (trifunctional enzyme subunit alpha, mitochondrial), an auxiliary component of dicer complex. Knockdown of GRP75 by respective siRNAs in Huh-7 cells resulted in the accumulation of dengue viral genomic RNA suggesting a role of GRP75 in regulating dengue virus replication in human cell lines. To elucidate the mode of action of GRP75, we over expressed the protein in Huh-7 cells and analysed the host miRNAs processing. The results revealed that, GRP75 is involved in processing of host miRNA, hsa-mir-126, that down regulates dengue virus replication. These findings suggest a regulatory role of human miRNA pathway especially GRP75 protein and hsa-mir-126 in dengue virus replication. These results thus provide insights into the role of miRNAs and RNAi machinery in dengue life cycle.
Insights
Researchers identified Glucose Regulated Protein 75kDa (GRP75) as a key host factor regulating Dengue virus replication. GRP75 influences host microRNA processing, specifically hsa-mir-126, which suppresses viral replication, offering new insights into RNAi pathways in Dengue infection.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- RNA interference (RNAi) is a crucial host defense mechanism against pathogen replication.
- Host microRNAs (miRNAs) are vital for cellular functions and viral infections.
- Understanding host factors influencing Dengue virus replication is critical for therapeutic strategies.
Purpose of the Study:
- To identify mammalian host factors involved in Dengue virus infection.
- To investigate the role of Glucose Regulated Protein 75kDa (GRP75) in Dengue virus replication.
- To elucidate the mechanism by which GRP75 affects viral replication through host miRNA processing.
Main Methods:
- Identification of host factors associated with the Dicer complex.
- siRNA-mediated knockdown of GRP75 in Huh-7 cells.
- Overexpression of GRP75 and analysis of host miRNA processing.
- Quantification of Dengue viral genomic RNA accumulation.
Main Results:
- GRP75 was identified as a host factor associated with the Dicer complex, specifically with HADHA.
- Knockdown of GRP75 led to increased Dengue viral genomic RNA, indicating its role in restricting viral replication.
- Overexpression of GRP75 demonstrated its involvement in processing of hsa-mir-126, a host miRNA that downregulates Dengue virus replication.
Conclusions:
- GRP75 is a significant host factor that regulates Dengue virus replication in human cells.
- The human miRNA pathway, involving GRP75 and hsa-mir-126, plays a regulatory role in Dengue virus replication.
- These findings provide novel insights into the interplay between RNAi machinery, host miRNAs, and the Dengue virus lifecycle.
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