Journal
ACS INFECTIOUS DISEASES
Volume 6, Issue 3, Pages 436-446Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.9b00384
Keywords
dengue virus; genome replication; innate immunity; defective interfering particle; nonstructural protein NS3; nonstructural protein NS5
Categories
Funding
- DARPA subcontract Interfering and Co-Evolving Prevention and Therapy [HR0011-17-2-0036]
- National Medical Research Council [NMRC/CBRG/0103/2016]
- Ministry of Health grant [MOH-000086 (MOH-OFIRG18-may-0006/2019)]
Ask authors/readers for more resources
Viral defective interfering particles (DIPs) with more than 90% of the genomic RNA (gRNA, similar to 11 000 nucleotides) deleted have been detected in sera from dengue patients. The DIP RNA contains stem-loop structures in the 5' and 3' end, which may permit RNA replication in the same manner as dengue virus (DENV) gRNA. Transfection of DENV2 infected human hepatoma cells with DIP RNA (DIP-296) resulted in significant inhibition of virus replication. DIP-296 RNA inhibited DENV replication in a dose-dependent manner in several cell lines tested. The mechanism of inhibition by DIP RNA is unclear; however, our studies imply that the retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) mediated innate immune antiviral signaling pathways and direct interactions of DIP RNA with viral replication proteins may be involved. The latter is supported by in vitro RNA electrophoretic mobility shift assays (REMSAs), which show that DIP RNA can bind directly to the DENV nonstructural proteins NS3 and NS5.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available