Abstract
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.
Highlights
Human amyloids have been shown to interact with viruses and interfere with viral replication
To investigate the potential for amyloids to interact with viruses encoding a homologous aggregation-prone regions (APRs), we here used a synthetic biology approach, using influenza A as a model virus
We present here the reverse engineering of synthetic amyloids that interact with a predefined target virus and reduce viral replication
Summary
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. Aggregation seeding, as observed for Aβ when binding to herpes virus, is a well-described process, driven by so-called aggregation-prone regions (APRs)[8] These APRs engage into homotypic interactions to form tightly packed intermolecular amyloid structures, resulting in a highly sequence-specific process[9,10,11,12], but allowing the interaction between proteins sharing highly homologous APRs. Interestingly, Aβ shares a homolog APR sequence with the envelope glycoprotein B4, a herpes protein for which an interaction with Aβ has already been shown[5]. Our results demonstrate that APRmediated amyloid interactions possess the same characteristics defining bona fide functional biological interactions including specificity and in vivo selectivity
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