Subgenomic RNA from Dengue Virus Type 2 Suppresses Replication of Dengue Virus Genomes and Interacts with Virus-Encoded NS3 and NS5 Proteins

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Wang, Sai
Chan, Kitti WK
Naripogu, Kishore B
Swarbrick, Crystall MD
Aaskov, John
Vasudevan, Subhash G
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2020
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Abstract

Viral defective interfering particles (DIPs) with more than 90% of the genomic RNA (gRNA, ∼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.

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ACS Infectious Diseases

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6

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3

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Subject

Biological sciences

Medical microbiology

defective interfering particle

dengue virus

genome replication

innate immunity

nonstructural protein NS3

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Wang, S; Chan, KWK; Naripogu, KB; Swarbrick, CMD; Aaskov, J; Vasudevan, SG, Subgenomic RNA from Dengue Virus Type 2 Suppresses Replication of Dengue Virus Genomes and Interacts with Virus-Encoded NS3 and NS5 Proteins, ACS Infectious Diseases, 2020, 6 (3), pp. 436-446

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