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TRIM5α restringe los poxvirus y es antagonizado por CypA y la proteína viral C6
Yiqi Zhao1,2, Yongxu Lu1,2, Samuel Richardson3
1Department of Pathology, University of Cambridge, Cambridge, UK.
Nature
|August 9, 2023
Resumen
TRIM5α humano (proteína del motivo tripartito 5α) restringe los ortopoxvirus uniéndose a su proteína L3 de la cápside. Las proteínas virales C6 y la ciclofilina A contrarrestan esto, pero los medicamentos como CsA los inhiben, ofreciendo un potencial antiviral.
Área de la Ciencia:
- Virología
- Inmunología
- Biología celular
Sus antecedentes:
- Se sabe que la proteína de motivo tripartito humano 5α (TRIM5α) restringe ciertos virus de ARN como el VIH.
- Su papel en la restricción de los virus del ADN, particularmente los ortopoxvirus, es menos conocido.
Objetivo del estudio:
- Investigar la actividad antiviral de TRIM5α contra los ortopoxvirus.
- Identificar las contramedidas virales y los objetivos terapéuticos potenciales.
Principales métodos:
- Se ha demostrado la restricción de TRIM5α de los ortopoxvirus a través de la unión del dominio SPRY a la proteína de la cápside L3.
- Se identificó la proteína viral C6 y la ciclofilina A (CypA) como factores contrarrestantes.
- Se evaluaron los efectos antivirales de la ciclosporina A (CsA) y sus derivados (alisporivir, NIM811) in vitro.
Principales resultados:
- TRIM5α restringe los ortopoxvirus al unirse a la proteína de la cápside L3, inhibiendo la replicación y activando la inmunidad innata.
- Los ortopoxvirus emplean C6 para degradar TRIM5α y CypA para antagonizar TRIM5α a través de la interacción L3.
- El CsA, el alisporivir y el NIM811 inhiben el CypA, demostrando actividad antiviral contra los ortopoxvirus dependientes del TRIM5α.
Conclusiones:
- TRIM5α actúa como un factor de restricción contra los ortopoxvirus.
- Las contramedidas virales implican la degradación de TRIM5α y el antagonismo por CypA.
- Los derivados de CsA son prometedores como terapias antivirales contra los ortopoxvirus debido a que se dirigen al factor huésped CypA, limitando la aparición de resistencia.
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