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1.
J Viral Hepat ; 24(5): 350-356, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28092420

RESUMEN

Hepatitis C virus (HCV) infection is currently the most important cause of chronic viral hepatitis in the world and one of the most frequent indications for liver transplantation. HCV uses different strategies to evade the innate and adaptive immune response, and this evasion plays a key role in determining viral persistence. Several HCV viral proteins have been described as immune modulators. In this review, we will focus on the effect of HCV nucleocapsid core protein in the function of immune cells and its correlation with the findings observed in HCV chronically infected patients. Effects on immune cell function related to both extracellular and intracellular HCV core localization will be considered. This review provides an updated perspective on the mechanisms involved in HCV evasion related to one single HCV protein, which could become a key tool in the development of new antiviral strategies able to control and/or eradicate HCV infection.


Asunto(s)
Hepacivirus/fisiología , Interacciones Huésped-Patógeno , Evasión Inmune , Terapia de Inmunosupresión , Proteínas del Núcleo Viral/metabolismo , Hepacivirus/inmunología , Hepacivirus/patogenicidad , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/virología , Humanos
2.
Genes Immun ; 15(7): 449-56, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25008862

RESUMEN

Linker for activation of T cells (LAT) is a transmembrane adaptor protein playing a key role in the development, activation and maintenance of peripheral homeostasis of T cells. In this study we identified a functional isoform of LAT. It originates from an intron 6 retention event generating an in-frame splice variant of LAT mRNA denoted as LATi6. Comparison of LATi6 expression in peripheral blood leukocytes of human and several other mammalian species revealed that it varied from being virtually absent in the mouse to being predominant in the cow. Analysis of LAT isoform frequency expressed from minigene splicing reporters carrying loss- or gain-of-function point mutations within intronic polyguanine sequences showed that these elements are critical for controlling the intron 6 removal. The protein product of LATi6 isoform (LATi6) ectopically expressed in LAT-deficient JCam 2.5 cell line localized correctly to subcellular compartments and supported T-cell receptor signaling but differed from the canonical LAT protein by displaying a shorter half-life and mediating an increased interleukin-2 secretion upon prolonged CD3/CD28 crosslinking. Altogether, our data suggest that the appearance of LATi6 isoform is an evolutionary innovation that may contribute to a more efficient proofreading control of effector T-cell response.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Empalme Alternativo , Proteínas de la Membrana/genética , Proteínas Adaptadoras Transductoras de Señales/química , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Secuencia de Bases , Línea Celular , Humanos , Intrones , Leucocitos/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Ratones , Datos de Secuencia Molecular , Mutación Puntual , Poli G/genética , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estabilidad Proteica , Transporte de Proteínas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especificidad de la Especie
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