RESUMEN
Pre-erythrocytic immunity to Plasmodium falciparum malaria is likely to be mediated by T-cell recognition of malaria epitopes presented on infected host cells via class I and II major histocompatibility complex (MHC) antigens. To test for associations of human leukocyte antigen (HLA) alleles with disease severity, we performed high-resolution typing of HLA class I and II loci and compared the distributions of alleles of HLA-A, -B, -C and -DRB1 loci in 359 Malian children of Dogon ethnicity with uncomplicated or severe malaria. We observed that alleles A*30:01 and A*33:01 had higher frequency in the group of patients with cerebral disease compared to patients with uncomplicated disease [A*30:01: gf = 0.2031 vs gf = 0.1064, odds ratio (OR) = 3.17, P = 0.004, confidence interval (CI) (1.94-5.19)] and [A*33:01: gf = 0.0781 vs gf = 0.0266, 4.21, P = 0.005, CI (1.89-9.84)], respectively. The A*30:01 and A*33:01 alleles share some sequence motifs and A*30:01 appears to have a unique peptide binding repertoire compared to other A*30 group alleles. Computer algorithms predicted malaria peptides with strong binding affinity for HLA-A*30:01 and HLA-A*33:01 but not to closely related alleles. In conclusion, we identified A*30:01 and A*33:01 as potential susceptibility factors for cerebral malaria, providing further evidence that polymorphism of MHC genes results in altered malaria susceptibility.
Asunto(s)
Antígenos HLA-A/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Malaria Falciparum/inmunología , Plasmodium falciparum/metabolismo , Adolescente , Algoritmos , Alelos , Niño , Preescolar , Predisposición Genética a la Enfermedad , Humanos , Lactante , Interleucina-10/genética , Leucocitos Mononucleares/citología , Malaria Falciparum/genética , Malí , Oportunidad Relativa , Polimorfismo GenéticoRESUMEN
Evolutionary homologs of the ets proto-oncogene have been discovered in the genomes of widely divergent eucaryote species from Drosophila to sea urchin to vertebrates. The prototype mammalian ets-1 and ets-2 genes are divided into three coding domains that differ in their rate of accumulation of sequence divergence. An analysis of sequence divergence of ets gene homologs in various species has produced a phylogenetic history of the ets gene family in the context of metazoan evolutionary radiation. A minimum of five duplication events of ets primordial genes were evident, namely (1) a duplication that separates primitive ets genes (Drosophila precursor of 74E, mouse PU.1 and human ELK1) from the ets-1, ets-2, erg ancestor; (2) and (3) two duplications that established separate ets, erg and elg/GABP-alpha lineages which occurred prior to invertebrate-vertebrate divergence; (4) divergence of ets-1 and ets-2 gene family also associated with vertebrate-invertebrate divergence; (5) duplication of ets-1 and ets-2 in Xenopus laevis to produce two ets-1 genes and two ets-2 genes during genomic tetraploidation in the recent ancestry of this species.
Asunto(s)
Proteínas Proto-Oncogénicas/genética , Proto-Oncogenes , Factores de Transcripción , Secuencia de Aminoácidos , Animales , Evolución Biológica , Drosophila , Humanos , Datos de Secuencia Molecular , Proto-Oncogenes Mas , Proteína Proto-Oncogénica c-ets-1 , Proteínas Proto-Oncogénicas c-ets , XenopusAsunto(s)
Proteínas de Unión al ADN , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proto-Oncogenes , Proteínas Represoras , Transactivadores , Factores de Transcripción , Xenopus laevis/genética , Animales , Datos de Secuencia Molecular , Polimorfismo Genético/genética , Proteína Proto-Oncogénica c-ets-2RESUMEN
A molecular clone of the Xenopus laevis ets-2 gene was isolated from an oocyte complementary DNA library. The amount of messenger RNA (mRNA) in each oocyte or embryo was almost constant during oogenesis and was maintained until the blastula stage of embryonic development, indicating that the observed 3.2-kilobase transcript is a maternal message. The only normal adult tissue in which ets-2 mRNA was detected was the ovary. Injection of antisense oligonucleotides homologous to the ets-2 sequence into oocytes led to degradation of the mRNA and blocked hormone-induced germinal vesicle breakdown. The ets-2 product is thus required for the meiotic maturation of Xenopus oocytes.
Asunto(s)
Proteínas de Unión al ADN , Oocitos/fisiología , Proteínas Proto-Oncogénicas/genética , Proto-Oncogenes , Proteínas Represoras , Transactivadores , Factores de Transcripción , Animales , División Celular , Embrión no Mamífero/fisiología , Femenino , Expresión Génica , Biblioteca de Genes , Oligonucleótidos Antisentido/farmacología , Oocitos/citología , Oocitos/efectos de los fármacos , Oogénesis , Proteínas Tirosina Quinasas/genética , Proteína Proto-Oncogénica c-ets-2 , ARN Mensajero/análisis , ARN Mensajero/genética , Transcripción Genética , Xenopus laevisRESUMEN
A previously-described herpes simplex virus type 2 DNA-binding protein with a molecular size of 38 kD has been further characterized. Using purified nucleocapsids, a DNase release assay, and intertypic recombinants, this protein was found to be a component of the nucleocapsid, intimately associated with the nuclear matrix, and encoded between 0.605 and 0.720 on the herpes simplex virus type 2 genome.
Asunto(s)
Cápside/análisis , Proteínas de Unión al ADN/análisis , Simplexvirus/análisis , Proteínas del Núcleo Viral/análisis , Proteínas Virales/análisis , Animales , Células Cultivadas , Cricetinae , Proteínas de Unión al ADN/genética , Electroforesis en Gel de Poliacrilamida , Genes Virales , Immunoblotting , Matriz Nuclear/microbiología , Plásmidos/genética , ARN Mensajero/genética , Células Vero , Proteínas Virales/genéticaRESUMEN
Western transfer and immunoenzymatic staining with affinity-purified monospecific antiserum was used to detect a 38-Kd protein that bound to native and denatured DNA cellulose. This protein has previously been shown to be a delayed early herpes simplex virus type-2 specific protein.