RESUMO
Objective: Most ZIKV infections occur in regions endemic for the related dengue virus (DENV). Anti-DENV antibodies have been demonstrated to cross-react with ZIKV. Some neutralize ZIKV infection while others mediate antibody-dependent enhancement (ADE), exacerbating ZIKV infection and complicating diagnosis of the etiologic agent. We aimed to characterize the humoral immune response in a ZIKV+, DENV- experienced individual in order to explore this anamnestic response and identify antibodies that may be useful in the development of therapeutic agents. Design and Methodology: Peripheral blood mononuclear cells (PBMCs) were collected from an individual (TT66) who was newly infected with ZIKV but had two previous DENV infections. Plasmablasts were isolated and analyses conducted using Atreca's Immune Repertoire CaptureTM technology. Monoclonal antibodies (mAbs) derived from TT66 during their acute and convalescent phase of ZIKV infection were screened in vitro for ZIKV and DENV binding and neutralization activity. Epitopes were then mapped using a shotgun mutagenesis approach. Results: We observed clonal expansion of two distinct antibody lineages representing 70% of total immunoglobulin sequences from TT66. We screened 18 mAbs representing two major lineages and five smaller families for neutralization and ADE between DENV and ZIKV. No highly typespecific mAbs were observed but rather a diverse pattern of neutralization, even within an individual lineage. Shotgun mutagenesis epitope mapping demonstrated epitopes for two of these broadly neutralizing mAb lineages lay within domain II ofE, close to the fusion loop. Conclusions: Results suggest that neutralizing antibody responses to ZIKV are extensively shaped by previous DENV exposure.
Assuntos
Humanos , Masculino , Feminino , Zika virus , Trinidad e Tobago , Linfócitos BRESUMO
PIP: A number of different theories exist to explain the working of the IUD. The present investigation is a study of the histological, histochemical, and ultrastructural changes in the female endometrium when the IUD is used, using samples of the uterine mucosa of women aged 22-38 (42 cases), taken 12 months after insertion of the IUD. The controls were samples of the same mucosa taken prior to IUD insertion. In 25 women the endometrium was in a proliferative phase; in 11 the endometrial stroma manifested focal infiltrates of lymphoid and histiocyte elements, occasionally with plasma cells; in 17 the endometrium was in the secreting phase. Histiochemical analysis of the proliferative phase revealed dust-like accumulation of glycogen in the glandular epithelium and in the stroma. In the phase of secretion the quantity of glycogen was somewhat lower than normal. In both phases of the menstrual cycle there was heightened acid phosphatase activity and lowered vitamin-C concentration. In 8 women the endometrium on the 9-13th days of the menstrual cycle was examined under an electron microscope. The endoplasm structure took the form of a moderately well developed system of canals and bubbles of various sizes concentrated mainly in the apical and peripheral sections of the cells. The Golgi apparatus was represented by a system of well developed narrow channels with bubbles and liquid deposits of various sizes. The mitochondria were small, round, or elongated, with a small number of imperfectly expressed cristae. These and other described changes in the endometrium point to a disturbance in the physiological rhythm of the menstrual cycle, which is confirmed by the discovery of large foci accumulations of glycogen granules in the epithelial cells in the phase of proliferation. There was also a certain deficiency in the secretory phase. The lower vitamin-C concentration makes the vascular walls more permeable and allows the stroma to leak out, which upsets the metabolic processes. The latter is intensified by the earlier onset of stromal fibrosis, especially in the surface endometrial layers. These endometrial changes evidently inhibit implantation of the ovum.^ieng
