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Evolución y actividad antiviral de una proteína humana de origen retroviral
John A Frank1, Manvendra Singh1, Harrison B Cullen1
1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Science (New York, N.Y.)
|October 27, 2022
Resumen
Los retrovirus endógenos humanos proporcionan una defensa contra las infecciones virales. Una proteína llamada Suppressyn, derivada de estos retrovirus, se expresa en el desarrollo humano temprano y restringe la infección retroviral.
Área de la Ciencia:
- La genómica
- Virología
- Inmunología
Sus antecedentes:
- Los genomas de los mamíferos contienen abundantes retrovirus endógenos (ERV) de infecciones antiguas.
- Las proteínas de la envoltura ERV en algunos mamíferos confieren protección contra los virus exógenos.
- Esta función protectora de las envolturas de ERV humanas expresadas endógenamente no está bien documentada.
Objetivo del estudio:
- Investigar el potencial de las secuencias retrovirales endógenas humanas para restringir la infección retroviral.
- Para caracterizar la función de una proteína derivada de la envoltura, Suppressyn, en la defensa del huésped.
Principales métodos:
- Análisis del genoma humano en busca de secuencias derivadas de la envoltura con potencial de restricción.
- Caracterización de la expresión de Suppressyn en los tejidos humanos.
- Ensayos de cultivo celular para comprobar la actividad antiviral de Suppressyn y sus homínidos ortólogos contra los retrovirus existentes.
Principales resultados:
- El genoma humano posee numerosas secuencias derivadas de la envoltura capaces de restringir la infección retroviral.
- Suppressyn se expresa en embriones humanos preimplantados y en la placenta a través de su promotor retroviral ancestral.
- Suppressyn y las proteínas hominoides relacionadas inhiben la infección por retrovirus de tipo D de mamíferos.
Conclusiones:
- Las proteínas de la envoltura retroviral endógena pueden ser cooptadas para la inmunidad del huésped y la defensa del genoma.
- Suppressyn representa un ejemplo funcional de defensa antiviral derivada de ERV en humanos.
- Este estudio apoya un modelo más amplio de utilización de la envoltura retroviral para la protección del huésped.
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