TRIM7 inhibits enterovirus replication and promotes emergence of a viral variant with increased pathogenicity.
Cell
; 184(13): 3410-3425.e17, 2021 06 24.
Article
em En
| MEDLINE
| ID: mdl-34062120
ABSTRACT
To control viral infection, vertebrates rely on both inducible interferon responses and less well-characterized cell-intrinsic responses composed of "at the ready" antiviral effector proteins. Here, we show that E3 ubiquitin ligase TRIM7 is a cell-intrinsic antiviral effector that restricts multiple human enteroviruses by targeting viral 2BC, a membrane remodeling protein, for ubiquitination and proteasome-dependent degradation. Selective pressure exerted by TRIM7 results in emergence of a TRIM7-resistant coxsackievirus with a single point mutation in the viral 2C ATPase/helicase. In cultured cells, the mutation helps the virus evade TRIM7 but impairs optimal viral replication, and this correlates with a hyperactive and structurally plastic 2C ATPase. Unexpectedly, the TRIM7-resistant virus has a replication advantage in mice and causes lethal pancreatitis. These findings reveal a unique mechanism for targeting enterovirus replication and provide molecular insight into the benefits and trade-offs of viral evolution imposed by a host restriction factor.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
/
Enterovirus
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Ubiquitina-Proteína Ligases
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Proteínas com Motivo Tripartido
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos