Fucoidan from Fucus vesiculosus can inhibit human norovirus replication by enhancing the host innate immune response

Abstract

• IFN signaling-related genes and ISGs upregulated in hNoV infected zebrafish larvae. • Fucoidan inhibited hNoV replication in zebrafish larvae. • Fucoidan enhanced the innate immune response of zebrafish larvae. Fucoidan extracted from Fucus vesiculosus was able to inhibit the replication of human noroviruses (hNoV) GII.4[P16] in zebrafish ( Danio rerio ) larvae. In the hNoV infected zebrafish larvae, a transcriptomic analysis showed significant upregulation (p < 0.01) of the interferons (IFNs) signaling related genes as well as a series of IFN-stimulated genes (ISGs) encoding antiviral effectors compared to the mock-infected controls. Accordingly, injection of fucoidan together with hNoV resulted in significant upregulation of 834 genes (p < 0.01) and the innate immune system was calculated as the top cluster with 94 gene counts involved and a log 10 (p) value of −25.41. Tulane virus (TV), a very commonly used surrogate for hNoV, served as a complementary tool showing that the fucoidan was not able to block the virions irreversibly. Enhancement of the host innate immune response could be one of the important mechanisms behind the anti-hNoV effect of fucoidan.