Back to Search
Start Over
Prevention of Measles Virus Infection by Intranasal Delivery of Fusion Inhibitor Peptides
- Source :
- Journal of Virology, Journal of Virology, American Society for Microbiology, 2015, 89 (2), pp.1143-1155. ⟨10.1128/JVI.02417-14⟩, Journal of Virology, 2015, 89 (2), pp.1143-1155. ⟨10.1128/JVI.02417-14⟩
- Publication Year :
- 2015
- Publisher :
- American Society for Microbiology, 2015.
-
Abstract
- Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV H and the fusion (F) envelope glycoprotein; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad-repeat (HR) regions of F can potently inhibit MV infection at the entry stage. We show here that specific features of H's interaction with its receptors modulate the susceptibility of MV F to peptide fusion inhibitors. A higher concentration of inhibitory peptides is required to inhibit F-mediated fusion when H is engaged to its nectin-4 receptor than when H is engaged to its CD150 receptor. Peptide inhibition of F may be subverted by continued engagement of receptor by H, a finding that highlights the ongoing role of H-receptor interaction after F has been activated and that helps guide the design of more potent inhibitory peptides. Intranasal administration of these peptides results in peptide accumulation in the airway epithelium with minimal systemic levels of peptide and efficiently prevents MV infectionin vivoin animal models. The results suggest an antiviral strategy for prophylaxis in vulnerable and/or immunocompromised hosts.IMPORTANCEMeasles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that parenterally delivered fusion-inhibitory peptides protect mice from lethal CNS MV disease. Here we show, using established small-animal models of MV infection, that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. Since the fusion inhibitors are stable at room temperature, this intranasal strategy is feasible even outside health care settings, could be used to protect individuals and communities in case of MV outbreaks, and could complement global efforts to control measles.
- Subjects :
- Male
Peptide
Inbred C57BL
Transgenic
Mice
Measle
Receptor
Viral Fusion Protein
chemistry.chemical_classification
Oligopeptide
Virus-Cell Interactions
3. Good health
Intranasal
Administration
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Oligopeptides
Immunology
Mice, Transgenic
Biology
Antiviral Agents
Chemoprevention
Microbiology
Measles
Measles virus
In vivo
Virology
medicine
Animals
Sigmodontinae
Administration, Intranasal
Antiviral Agent
Animal
Virus Internalization
biology.organism_classification
medicine.disease
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Mice, Inbred C57BL
Disease Models, Animal
chemistry
Insect Science
Measles viru
Disease Models
Nasal administration
Measles vaccine
Viral Fusion Proteins
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....0b5ea17a4cd7b493fd109ae26c4a0f8d