Peptide inhibitors of tembusu virus infection derived from the envelope protein

Abstract

The outbreak and spread of Tembusu virus (TMUV) has caused very large losses in the waterfowl-breeding industry since 2010. The viral envelope (E) protein, the principal surface protein of viral particles, plays a vital role in viral entry and fusion. In this study, two peptides derived from domain II (DII) and the stem of the TMUV envelope protein, TP1 and TP2, respectively, were tested for their antiviral activity. TP1 and TP2 inhibited TMUV infection in BHK-21 cells, and their 50% inhibitory concentrations (IC 50 ) were 14.19 mg/L and 7.64 mg/ L, respectively. Viral inhibition assays in different cell lines of avian origin showed that the inhibitory effects of TP1 and TP2 are not cell type dependent. Moreover, TP2 also exhibited inhibitory activity against Japanese encephalitis virus (JEV) infection. The two peptides inhibited antibody-mediated TMUV infection of duck peripheral blood lymphocytes. Co-immunoprecipitation assays and indirect enzyme-linked immunosorbent assays (ELISAs) indicated that both peptides interact with the surface of the TMUV virion. RNase digestion assays confirmed the release of viral RNA following incubation with TP1, while incubation with TP1 or TP2 interfered with the binding between TMUV and cells. Taken together, these results show that TP1 and TP2 may be developed into antiviral treatments against TMUV infection.

Innate immune responses to duck Tembusu virus infection

“…Therefore, the viral RNA genome was translated to initiate virus replication, at the same time the ubiquitin-proteasome system also played an important role in DTMUV replication [ 49 ]. In addition to mediating virus entry, E protein is essential for DTMUV pathogenesis [ 50 ]; especially, mutations in several important amino acid sites, which can significantly affect viral pathogenicity. Yan et al reported that a single mutation at amino acid residue 156 (S-P) reduced the ability of viral replication and transmission in ducks, and further analysis confirmed that the potential mechanism was composed by the disruption of N-linked glycosylation at position 154 and changes in the conformation of the “150 loop” of the E protein [ 51 ].…”

Review of antiviral peptides for use against zoonotic and selected non-zoonotic viruses

“…In the case of TP2, this peptide showed antiviral activity against TMUV as well as Japanese encephalitis virus (another Flaviviridae virus), and due to the highly conserved stem regions of TMUV and other flaviviruses, TP2 may probably inhibit other flaviviruses. Therefore, TP2 and TP2 derivatives or analogous peptides might probably work as broad-spectrum flavivirus inhibitors [85].…”