Skip to Main content Skip to Navigation
Journal articles

Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein.

Simona Ozden 1 Marianne Lucas-Hourani 2 Pierre-Emmanuel Ceccaldi 1 Ajoy Basak 3 Menogh Valentine 3 Suzanne Benjannet 4 Josée Hamelin 4 Yves Jacob 5 Kamel Mamchaoui 6 Vincent Mouly 6 Philippe Desprès 7 Antoine Gessain 1 Gillian Butler-Browne 6, 8 Michel Chrétien 4 Frédéric Tangy 2 Pierre-Olivier Vidalain 2 Nabil G. Seidah 4, *
* Corresponding author
1 Epidémiologie et Physiopathologie des Virus Oncogènes
2 Génomique Virale et Vaccination
3 Regional Protein Chemistry Center
4 Biochemical Neuroendocrinology
5 Génétique, Papillomavirus et Cancer Humain
6 Groupe Myologie
7 Interactions Moléculaires Flavivirus-Hôtes
8 UMR S 787
Abstract : Chikungunya virus (CHIKV) is a mosquito-transmitted Alphavirus that causes in humans an acute infection characterized by polyarthralgia, fever, myalgia, and headache. Since 2005 this virus has been responsible for an epidemic outbreak of unprecedented magnitude. By analogy with other alphaviruses, it is thought that cellular proteases are able to process the viral precursor protein E3E2 to produce the receptor-binding E2 protein that associates as a heterodimer with E1. Destabilization of the heterodimer by exposure to low pH allows viral fusion and infection. We show that among a large panel of proprotein convertases, membranous furin but also PC5B can process E3E2 from African CHIKV strains at the HRQRR(64) / ST site, whereas a CHIKV strain of Asian origin is cleaved at RRQRR(64) / SI by membranous and soluble furin, PC5A, PC5B, and PACE4 but not by PC7 or SKI-1. Using fluorogenic model peptides and recombinant convertases, we observed that the Asian strain E3E2 model peptide is cleaved most efficiently by furin and PC5A. This cleavage was also observed in CHIKV-infected cells and could be blocked by furin inhibitor decanoyl-RVKR-chloromethyl ketone. This inhibitor was compared with chloroquine for its ability to inhibit CHIKV spreading in myoblast cell cultures, a cell-type previously described as a natural target of this virus. Our results demonstrate the role of furin-like proteases in the processing of CHIKV particles and point out new approaches to inhibit this infection.
Document type :
Journal articles
Complete list of metadatas

Cited literature [33 references]  Display  Hide  Download
https://hal-pasteur.archives-ouvertes.fr/pasteur-00330695
Contributor : Mireille Gau <>
Submitted on : Wednesday, October 15, 2008 - 3:54:40 PM
Last modification on : Wednesday, August 19, 2020 - 11:16:36 AM
Long-term archiving on: : Saturday, November 26, 2016 - 2:15:59 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

PASTEUR | CNRS | UPMC | CEA | SORBONNE-UNIVERSITE | UP-SCIENCES

Citation

Simona Ozden, Marianne Lucas-Hourani, Pierre-Emmanuel Ceccaldi, Ajoy Basak, Menogh Valentine, et al.. Inhibition of Chikungunya virus infection in cultured human muscle cells by furin inhibitors: impairment of the maturation of the E2 surface glycoprotein.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (32), pp.21899-908. ⟨10.1074/jbc.M802444200⟩. ⟨pasteur-00330695⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

310