Antiviral action of nitric oxide on dengue virus type 2 replication.
Recently, nitric oxide (NO) has been shown to suppress dengue virus (DENV) RNA and protein accumulation in infected cells. In this report, the potential target of the inhibitory effect of NO was studied at the molecular level. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), showed an inhibitory effect on RNA accumulation at around 8-14 h post-infection, which corresponded to the step of viral RNA synthesis in the DENV life cycle. The activity of the viral replicase isolated from SNAP-treated DENV-2-infected cells was suppressed significantly compared with that of the negative-control N-acetyl-DL-penicillamine (NAP)-treated cells. Further investigations on the molecular target of NO action showed that the activity of recombinant DENV-2 NS5 in negative-strand RNA synthesis was affected in the presence of 5 mM SNAP in in vitro RNA-dependent RNA polymerase (RdRp) assays, whereas the RNA helicase activity of DENV-2 NS3 was not inhibited up to a concentration of 15 mM SNAP. These results suggest that the inhibitory effect of NO on DENV infection is partly via inhibition of the RdRp activity, which then downregulates viral RNA synthesis.
Takhampunya
Ratree
R
Department of Microbiology, Faculty of Science, Mahidol University, 272 Rama VI Road, Bangkok 10400, Thailand.
Padmanabhan
R
R
Department of Microbiology and Immunology, Georgetown University, School of Medicine, Washington DC, USA.
Ubol
Sukathida
S
Department of Microbiology, Faculty of Science, Mahidol University, 272 Rama VI Road, Bangkok 10400, Thailand.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D009033:Culicidae; D003716:Dengue Virus / Q000187:drug effects* / Q000502:physiology*; D000882:Haplorhini; D009569:Nitric Oxide / Q000494:pharmacology*; D011485:Protein Binding; D020365:RNA Helicases / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D009569:Nitric Oxide; D020365:RNA Helicases