BIOLOGY OF PEDIATRIC HEPATITIS C INFECTION

小儿丙型肝炎感染的生物学

• 批准号: 6150425
• 负责人: William Borkowsky
• 金额: $ 46.92万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-15 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6150425
• 关键词: CD4 molecule; HIV infections; alleles; cellular immunity; clinical research; enzyme linked immunosorbent assay; gel mobility shift assay; hepatitis C; hepatitis C virus; histocompatibility antigens; human immunodeficiency virus; human pregnant subject; humoral immunity; immunogenetics; immunoregulation; liver function; newborn human (0-6 weeks); nucleic acid sequence; pathologic process; pediatric AIDS; placental transfer; polymerase chain reaction; serology /serodiagnosis; statistics /biometry; vertical transmission

DESCRIPTION (Adapted from the Investigator's Abstract): The goal of this proposal is to study the factors influencing the transmission of hepatitis C (HCV) from HIV- and HCV-infected mothers to their offspring, describing the natural history of this process, including the virologic, immunologic, and the genetic factors at play in both preventing transmission and modifying any infection which is not prevented. The following aims are planned: AIM 1) To describe the natural history of infection by identifying HCV-infected pregnant women and studying their offspring for evidence of HCV infection. This will include the quantitation of HCV during pregnancy in cell-free and cell-associated blood compartments, quantitation of CD4 and HIV viral load, and their correlation with whether HCV transmission occurs. The offspring will be studied prospectively from birth for evidence of HCV infection using PCR and serologic methodologies. The transmission rate in children born to HIV-uninfected mothers will be compared to that in HIV-infected and -uninfected children born to HIV-infected mothers. The effect of HCV infection on liver function will be measured. AIM 2) To assess the distribution of quasispecies using the heteroduplex mobility assay on plasma and peripheral blood mononuclear cells from HCV-infected mothers during pregnancy, peripartum, and in their respective HCV-infected children. This will determine whether the child is infected with a selected few or unselected viruses present in the mother. AIM 3) To measure humoral and cell-mediated responses to HCV in both HCV infected and uninfected children born to infected mothers prospectively from birth. The presence or absence of such responses will be correlated with infection status and disease status. The presence or absence of these responses will be correlated with viral diversification that occurs in the child as described in AIM 2. AIM 4) To determine the HLA status of the HCV-infected mothers and their offspring. The prevalence of alleles in the mother and child will be correlated with whether transmission of HCV occurs. The influence of both maternal and child alleles on transmission will be assessed. The correlation of immune responses measured in AIM 3 and the clinical outcome of HCV infection with HLA alleles in the child will be studied.

描述（根据调查员的摘要改编）：目的 提案是研究影响丙型肝炎传播的因素 （HCV）从HIV和HCV感染的母亲到其后代，描述 这个过程的自然历史，包括病毒学，免疫学和 防止传输和修饰的遗传因素 任何没有阻止的感染。 计划以下目标：目标 1）通过识别感染HCV的感染来描述感染的自然史 孕妇并研究其后代，以证明HCV感染的证据。 这将包括无细胞和无细胞怀孕期间的HCV定量 与细胞相关的血室，定量CD4和HIV病毒负荷， 以及它们与HCV传播是否发生的相关性。 后代 将从出生开始研究，以证明使用HCV感染 PCR和血清学方法。 出生的孩子的传播率 将艾滋病毒未感染的母亲与艾滋病毒感染的母亲进行比较 - 未感染的儿童是艾滋病毒感染的母亲。 HCV的效果 将测量对肝功能的感染。 目标2）评估 使用异源迁移率测定等离子体上的准蛋白酶分布 以及来自HCV感染母亲的外周血单核细胞 怀孕，周围的围产社及其各自的HCV感染儿童。 这 将确定孩子是否感染了少数或 母亲中存在未选择的病毒。 目标3）测量体液和 细胞介导的对HCV感染和未感染儿童的HCV的反应 从出生开始就出生于感染的母亲。 存在或不存在 这种反应将与感染状况和疾病有关 地位。 这些响应的存在或不存在将与 如AIM 2所述，在儿童中发生的病毒多样化。 4）确定HCV感染的母亲的HLA状态及其 后代。 母亲和孩子等位基因的流行率将会 与HCV的传播是否发生相关。 两者的影响 将评估传播的母亲和儿童等位基因。 这 在AIM 3和临床结果中测得的免疫反应的相关性 将研究儿童中HLA等位基因的HCV感染。