A novel peptide derived from the fusion protein heptad repeat inhibits replication of subacute sclerosing panencephalitis virus in vitro and in vivo

Masahiro Watanabe, Koichi Hashimoto, Yusaku Abe, Eiichi N. Kodama, Ryota Nabika, Shinya Oishi, Shinichiro Ohara, Masatoki Sato, Yukihiko Kawasaki, Nobutaka Fujii, Mitsuaki Hosoya

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Subacute sclerosing panencephalitis (SSPE) is a persistent, progressive, and fatal degenerative disease resulting from persistent measles virus (MV) infection of the central nervous system. Most drugs used to treat SSPE have been reported to have limited effects. Therefore, novel therapeutic strategies are urgently required. The SSPE virus, a variant MV strain, differs virologically from wild-typeMV strain. One characteristic of the SSPE virus is its defective production of cell-free virus, which leaves cell-to-cell infection as the major mechanism of viral dissemination. The fusion protein plays an essential role in this cell-tocell spread. It contains two critical heptad repeat regions that forma six-helix bundle in the trimer similar to most viral fusion proteins. In the case of human immunodeficiency virus type-1 (HIV-1), a synthetic peptide derived from the heptad repeat region of the fusion protein enfuvirtide inhibits viral replication and is clinically approved as an anti-HIV-1 agent. The heptad repeat regions of HIV-1 are structurally and functionally similar to those of the MV fusion protein.We therefore designed novel peptides derived from the fusion protein heptad repeat region of the MV and examined their effects on the measles and SSPE virus replication in vitro and in vivo. Some of these synthetic novel peptides demonstrated high antiviral activity against both the measles (Edmonston strain) and SSPE (Yamagata-1 strain) viruses at nanomolar concentrations with no cytotoxicity in vitro. In particular, intracranial administration of one of the synthetic peptides increased the survival rate from 0% to 67% in an SSPE virus-infected nude mouse model.

Original languageEnglish
Article numbere0162823
JournalPloS one
Volume11
Issue number9
DOIs
Publication statusPublished - 2016 Sep

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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