1. Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication
- Author
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Lei Bao, Chun Li, Shan-Shan Guo, Ronghua Zhao, Jing Sun, and Xiaolan Cui
- Subjects
Male ,0301 basic medicine ,Eukaryotic Initiation Factor-2 ,Administration, Oral ,lcsh:Medicine ,Virus Replication ,medicine.disease_cause ,Mice ,0302 clinical medicine ,Influenza A virus ,Phosphorylation ,lcsh:Science ,Polymerase ,Host factor ,Multidisciplinary ,biology ,Drug development ,Antivirals ,RNA-Binding Proteins ,Gardenia ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,RNA, Viral ,Female ,Pact ,Antiviral Agents ,Article ,Virus ,Viral Proteins ,03 medical and health sciences ,Influenza, Human ,medicine ,Animals ,Humans ,A549 cell ,Plant Extracts ,lcsh:R ,RNA-Dependent RNA Polymerase ,Protein kinase R ,Virology ,In vitro ,Disease Models, Animal ,030104 developmental biology ,A549 Cells ,Fruit ,Iridoid Glycosides ,biology.protein ,lcsh:Q - Abstract
Epidemic and pandemic influenza A virus (IAV) poses a significant threat to human populations worldwide. Iridoid glycosides are principal bioactive components from the Gardenia jasminoides J. Ellis fruit that exhibit antiviral activity against several strains of IAV. In the present study, we evaluated the protective effect of Fructus Gardeniae iridoid glycoside extracts (IGEs) against IAV by cytopathogenic effect(CPE), MTT and a plaque formation assay in vitro and examined the reduction in the pulmonary index (PI), restoration of body weight, reduction in mortality and increases in survival time in vivo. As a host factor, PACT provides protection against the pathogenic influenza A virus by interacting with IAV polymerase and activating the IFN-I response. To verify the whether IGEs suppress IAV replication in a PACT-dependent manner, IAV RNA replication, expression of PACT and the phosphorylation of eIF2α in A549 cells were detected; the levels of IFNβ, PACT and PKR in mouse lung tissues were determined; and the activity of IAV polymerase was evaluated in PACT-compromised cells. The results indicated that IGEs sufficiently alleviated cell damage and suppressed IAV replication in vitro, protecting mice from IAV-induced injury and lethal IAV infection. These anti-IAV effects might be related to disrupted interplay between IVA polymerase and PACT and/or prevention of a PACT-dependent overactivated IFN-I antiviral response. Taken together, our findings reveal a new facet of the mechanisms by which IGEs fight the influenza A virus in a PACT-dependent manner.
- Published
- 2020