Oligomeric procyanidins stimulate innate antiviral immunity (154.9)

Abstract

Abstract Oligomeric procyanidins (OPCs) have been shown to have antiviral and immunostimulatory effects. OPCs isolated from non-ripe apple peel, found in the dietary supplement Applepoly®, were tested for capacity to reduce dengue virus (DENV) titers. Similar to published accounts, OPCs exhibited direct antiviral activity. OPCs also enhanced expression of critical innate antiviral products during DENV infection of human PBMCs. Specifically, expression of MXI and IFNB transcripts in DENV infected cells, and phosphorylation of STAT2 in response to recombinant type I IFN (IFN I), were increased by OPC treatment. During low MOI infection, addition of OPCs also increased expression of STAT1 transcripts, MHC I and TNFα protein production. Thus, OPCs exhibited innate immune stimulation of DENV-infected human cells, bystander cells in infected cultures, and uninfected cells treated with IFN I. To test the effects of OPC ingestion in vivo, mice were fed a rich source of OPCs and injected with polyIC to mimic innate responses to viral infection. Ingestion of OPCs resulted in enhanced innate antiviral responses in vivo. While OPCs from a number of sources are known to exhibit antiviral effects, their mechanisms are not precisely defined. The capacity of OPCs to enhance innate antiviral immunity could be broadly applicable to many viral infections and two separate antiviral mechanisms, direct and immunomodulatory, suggest that OPCs may represent a novel, robust antiviral therapy.