TY  - JOUR
AU  - Michiels, Emiel
AU  - Roose, Kenny
AU  - Gallardo, Rodrigo
AU  - Khodaparast, Ladan
AU  - Khodaparast, Laleh
AU  - van der Kant, Rob
AU  - Siemons, Maxime
AU  - Houben, Bert
AU  - Ramakers, Meine
AU  - Wilkinson, Hannah
AU  - Guerreiro, Patricia
AU  - Louros, Nikolaos
AU  - Kaptein, Suzanne J F
AU  - Ibañez, Lorena Itatí
AU  - Smet, Anouk
AU  - Baatsen, Pieter
AU  - Liu, Shu
AU  - Vorberg, Ina
AU  - Bormans, Guy
AU  - Neyts, Johan
AU  - Saelens, Xavier
AU  - Rousseau, Frederic
AU  - Schymkowitz, Joost
TI  - Reverse engineering synthetic antiviral amyloids.
JO  - Nature Communications
VL  - 11
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2020-01310
SP  - 2832
PY  - 2020
AB  - 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.
KW  - Amyloid: genetics
KW  - Amyloid: pharmacology
KW  - Amyloid: therapeutic use
KW  - Animals
KW  - Antiviral Agents: pharmacology
KW  - Antiviral Agents: therapeutic use
KW  - Disease Models, Animal
KW  - Dogs
KW  - Female
KW  - HEK293 Cells
KW  - Host-Pathogen Interactions: drug effects
KW  - Humans
KW  - Influenza A virus: drug effects
KW  - Influenza A virus: genetics
KW  - Influenza A virus: pathogenicity
KW  - Influenza, Human: drug therapy
KW  - Influenza, Human: virology
KW  - Madin Darby Canine Kidney Cells
KW  - Mice
KW  - Polymorphism, Genetic
KW  - Recombinant Proteins: genetics
KW  - Recombinant Proteins: pharmacology
KW  - Recombinant Proteins: therapeutic use
KW  - Reverse Genetics: methods
KW  - Synthetic Biology: methods
KW  - Viral Proteins: genetics
KW  - Viral Proteins: metabolism
KW  - Virus Replication: drug effects
KW  - Zika Virus: drug effects
KW  - Zika Virus: genetics
KW  - Zika Virus: pathogenicity
KW  - Zika Virus Infection: drug therapy
KW  - Zika Virus Infection: virology
KW  - Amyloid (NLM Chemicals)
KW  - Antiviral Agents (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - Viral Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32504029
C2  - pmc:PMC7275043
DO  - DOI:10.1038/s41467-020-16721-8
UR  - https://pub.dzne.de/record/153313
ER  -