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Ebolavirus -Peptide Immunoadhesins Inhibit Marburgvirus and Ebolavirus Cell Entry
- Source :
- Journal of Virology
- Publication Year :
- 2011
- Publisher :
- American Society for Microbiology, 2011.
-
Abstract
- With the exception of Reston and Lloviu viruses, filoviruses (marburgviruses, ebolaviruses, and “cuevaviruses”) cause severe viral hemorrhagic fevers in humans. Filoviruses use a class I fusion protein, GP 1,2 , to bind to an unknown, but shared, cell surface receptor to initiate virus-cell fusion. In addition to GP 1,2 , ebolaviruses and cuevaviruses, but not marburgviruses, express two secreted glycoproteins, soluble GP (sGP) and small soluble GP (ssGP). All three glycoproteins have identical N termini that include the receptor-binding region (RBR) but differ in their C termini. We evaluated the effect of the secreted ebolavirus glycoproteins on marburgvirus and ebolavirus cell entry, using Fc-tagged recombinant proteins. Neither sGP-Fc nor ssGP-Fc bound to filovirus-permissive cells or inhibited GP 1,2 -mediated cell entry of pseudotyped retroviruses. Surprisingly, several Fc-tagged Δ-peptides, which are small C-terminal cleavage products of sGP secreted by ebolavirus-infected cells, inhibited entry of retroviruses pseudotyped with Marburg virus GP 1,2 , as well as Marburg virus and Ebola virus infection in a dose-dependent manner and at low molarity despite absence of sequence similarity to filovirus RBRs. Fc-tagged Δ-peptides from three ebolaviruses (Ebola virus, Sudan virus, and Taï Forest virus) inhibited GP 1,2 -mediated entry and infection of viruses comparably to or better than the Fc-tagged RBRs, whereas the Δ-peptide-Fc of an ebolavirus nonpathogenic for humans (Reston virus) and that of an ebolavirus with lower lethality for humans (Bundibugyo virus) had little effect. These data indicate that Δ-peptides are functional components of ebolavirus proteomes. They join cathepsins and integrins as novel modulators of filovirus cell entry, might play important roles in pathogenesis, and could be exploited for the synthesis of powerful new antivirals.
- Subjects :
- viruses
Recombinant Fusion Proteins
Immunology
Biology
medicine.disease_cause
Microbiology
Antiviral Agents
Virus
Cell Line
Marburg virus
Viral Proteins
Virology
medicine
Animals
Humans
Ebolavirus
chemistry.chemical_classification
Biological Products
Ebola virus
Virus Internalization
Marburgvirus
biology.organism_classification
Fusion protein
Bundibugyo virus
Immunoglobulin Fc Fragments
Virus-Cell Interactions
chemistry
Insect Science
Glycoprotein
Subjects
Details
- ISSN :
- 0022538X
- Volume :
- 85
- Issue :
- 17
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....8e31adce4ceae0cdc214dc33c9810386
- Full Text :
- https://doi.org/10.1128/jvi.02600-10