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El origen genético híbrido crea proteínas quiméricas de virus humanos durante la infección
Jessica Sook Yuin Ho1, Matthew Angel2, Yixuan Ma1
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cell
|June 20, 2020
Resumen
Los virus de ARN generan nuevos genes híbridos a través de un mecanismo dependiente del huésped llamado "arranque". Este proceso crea mRNAs virales humanos quiméricos, que conducen a nuevas proteínas virales y contribuyen a la virulencia de la enfermedad.
Área de la Ciencia:
- Virología
- Biología molecular
- La genética
Sus antecedentes:
- Los virus de ARN representan un riesgo significativo para la salud.
- La replicación viral a menudo se basa en el ARNm del huésped, utilizando un proceso llamado cap-snatching.
- El cap-snatching involucra a las polimerasas virales que dividen las transcripciones del huésped para iniciar la síntesis del ARNm viral.
Objetivo del estudio:
- Investigar el potencial para la generación de ARNm quimérico humano-viral.
- Identificar nuevos mecanismos de origen genético durante las infecciones virales.
- Para explorar las consecuencias funcionales de tales transcripciones quiméricas.
Principales métodos:
- Hipotetizó la existencia de un mecanismo de arranque.
- Analizó la expresión genética viral y del huésped en las células infectadas.
- Investigó los productos de traducción de los ARNm quiméricos.
- Se evaluaron las respuestas de las células T a las nuevas proteínas virales.
Principales resultados:
- Se confirmó la existencia de "arrastre inicial" en las células infectadas por el virus de la influenza A (IAV).
- Demostró la creación de ARNm quiméricos humanos-virales con potencial de codificación.
- Se identificaron proteínas virales N-terminalmente extendidas y nuevos polipéptidos mediante sobreimpresión genética.
- Se demostró que estas proteínas quiméricas provocan respuestas de las células T y contribuyen a la virulencia del VAI.
Conclusiones:
- Un mecanismo dependiente del huésped, el "arrastre inicial", permite la génesis de genes híbridos durante las infecciones virales.
- Este mecanismo contribuye a la virulencia viral mediante la generación de nuevas proteínas.
- Los hallazgos tienen implicaciones para la comprensión de la evolución y la patogénesis de los virus de ARN en humanos, animales y plantas.
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