Reverse engineering synthetic antiviral amyloids.

Amyloid / genetics Animals Antiviral Agents / pharmacology Disease Models, Animal Dogs Female HEK293 Cells Host-Pathogen Interactions / drug effects Humans Influenza A virus / drug effects Influenza, Human / drug therapy Madin Darby Canine Kidney Cells Mice Polymorphism, Genetic Recombinant Proteins / genetics Reverse Genetics / methods Synthetic Biology / methods Viral Proteins / genetics Virus Replication / drug effects Zika Virus / drug effects Zika Virus Infection / drug therapy

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
05 06 2020

Historique:

received: 21 06 2019

accepted: 12 05 2020

entrez: 7 6 2020

pubmed: 7 6 2020

medline: 22 8 2020

Statut: epublish

Résumé

Human amyloids have been shown to interact with viruses and interfere with viral replication. Based on this observation, we employed a synthetic biology approach in which we engineered virus-specific amyloids against influenza A and Zika proteins. Each amyloid shares a homologous aggregation-prone fragment with a specific viral target protein. For influenza we demonstrate that a designer amyloid against PB2 accumulates in influenza A-infected tissue in vivo. Moreover, this amyloid acts specifically against influenza A and its common PB2 polymorphisms, but not influenza B, which lacks the homologous fragment. Our model amyloid demonstrates that the sequence specificity of amyloid interactions has the capacity to tune amyloid-virus interactions while allowing for the flexibility to maintain activity on evolutionary diverging variants.

Identifiants

DOI: 10.1038/s41467-020-16721-8 PMID: 32504029 PMC: PMC7275043

pubmed: 32504029

doi: 10.1038/s41467-020-16721-8

pii: 10.1038/s41467-020-16721-8

pmc: PMC7275043

doi:

Substances chimiques

Amyloid 0

Antiviral Agents 0

Recombinant Proteins 0

Viral Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

2832

Commentaires et corrections

Type : ErratumIn

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