Experimental Evolution Reveals a Genetic Basis for Membrane-Associated Virus Release.
Mol Biol Evol
; 38(2): 358-367, 2021 01 23.
Article
em En
| MEDLINE
| ID: mdl-32810259
ABSTRACT
Many animal viruses replicate and are released from cells in close association to membranes. However, whether this is a passive process or is controlled by the virus remains poorly understood. Importantly, the genetic basis and evolvability of membrane-associated viral shedding have not been investigated. To address this, we performed a directed evolution experiment using coxsackievirus B3, a model enterovirus, in which we repeatedly selected the free-virion or the fast-sedimenting membrane-associated viral subpopulations. The virus responded to this selection regime by reproducibly fixing a series of mutations that altered the extent of membrane-associated viral shedding, as revealed by full-genome ultra-deep sequencing. Specifically, using site-directed mutagenesis, we showed that substitution N63H in the viral capsid protein VP3 reduced the ratio of membrane-associated to free viral particles by 2 orders of magnitude. These findings open new avenues for understanding the mechanisms and implications of membrane-associated viral transmission.
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Base de dados:
MEDLINE
Assunto principal:
Eliminação de Partículas Virais
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Enterovirus Humano B
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Proteínas do Capsídeo
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article