RESUMEN
The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-1α is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions. In this study, we analyzed the expression of host HNF-1α in relation to malaria infection and evaluated its interaction with the 5'-untranslated region of subtilisin-like protease 2 (subtilase, Sub2). Recombinant human HNF-1α expressed by a lentiviral vector (LV HNF-1α) was introduced into mice. Interestingly, differences in the activity of the 5'-untranslated region of the Pf-Sub2 promoter were detected in 293T cells, and LV HNF-1α was observed to influence promoter activity, suggesting that host HNF-1α interacts with the Sub2 gene.
Asunto(s)
Regiones no Traducidas 5'/genética , Regulación de la Expresión Génica/genética , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Subtilisinas/genética , Animales , Línea Celular , ADN Protozoario/genética , Vectores Genéticos , Factor Nuclear 1-alfa del Hepatocito/administración & dosificación , Factor Nuclear 1-alfa del Hepatocito/genética , Interacciones Huésped-Parásitos , Humanos , Inyecciones Intravenosas , Lentivirus/genética , Malaria Falciparum/metabolismo , Malaria Falciparum/patología , Ratones , Plasmodium falciparum/efectos de los fármacos , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética , ARN Protozoario/genética , Proteínas Recombinantes , Transducción de Señal , Subtilisinas/metabolismoRESUMEN
The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-1alpha is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions. In this study, we analyzed the expression of host HNF-1alpha in relation to malaria infection and evaluated its interaction with the 5'-untranslated region of subtilisin-like protease 2 (subtilase, Sub2). Recombinant human HNF-1alpha expressed by a lentiviral vector (LV HNF-1alpha) was introduced into mice. Interestingly, differences in the activity of the 5'-untranslated region of the Pf-Sub2 promoter were detected in 293T cells, and LV HNF-1alpha was observed to influence promoter activity, suggesting that host HNF-1alpha interacts with the Sub2 gene.
