NICHD Small Grants Programs

描述（由申请人提供）：围产期传播占儿童艾滋病毒感染的90%以上。 深入了解宿主免疫基因反应（如趋化因子，细胞因子，HLA多态性）的分子和遗传学机制，影响病原体和宿主-HIV-1相互作用的传播后果，对于公共卫生的诊断，传播和预防策略的各个方面都是至关重要的。 本研究的目的是了解HLA-G基因突变在HIV-1感染妇女将病毒传播给婴儿的可能性增加（或减少）中的作用。HLA-G是一种非经典的1类MHC基因，在母胎界面的绒毛外细胞滋养层细胞中高度表达。 具体目标：进一步研究HLA-G外显子2突变的潜在作用，该突变先前与围产期传播风险降低相关（Aikhionbare，AIDS 2001，15：2196-8）和从项目RETRO-C1，01 BP 1712，10阿比让科特迪瓦和围产期艾滋病协同传播研究，研究新生儿对艾滋病毒1-围产期传播的易感性可能增加或减少。方法：将从HIV-1感染和未感染的母婴对中获取DNA样本，作为项目RETRO-C1，01 BP 1712，10 Abidjan Cote d 'Ivoire和围产期艾滋病协作传播研究的一部分，将通过以下技术进行筛查：WAVETM核酸片段分析，等位基因特异性聚合酶链反应（PCR），单链构象多态性（SSCP），然后进行DNA克隆/测序。将对本研究的分子数据进行Fisher精确检验、最大似然、关联不平衡参数、比值比、相对风险分析和组值。这些结果将为艾滋病病毒致病的基本机制，特别是某些宿主遗传因素对HIV-1围产期感染的贡献提供新的见解。

DESCRIPTION (provided by applicant): Perinatal transmission accounts for more than 90 percent of HIV-infection in children. A thorough understanding of the molecular and genetics mechanisms of the host immune gene response (such as chemokines, cytokines, HLA polymorphisms) effecting the pathogens and transmission consequences of host-HIV-1 interactions is essential to all aspects of public health for diagnostic, transmission, and prevention strategies. This study is designed to understand the mutational role of HLA-G gene that make HIV-1 infected women more (or less likely) to transmit virus to her infant. HLA-G is non-classical class 1 MHC gene and it is highly expressed in extravillous cytotrophoblast at the maternal fetal interface. Specific aim: To further examine the potential role (s) of the mutation in HLA-G exon 2, which was previously associated to reduced risk in perinatal transmission (Aikhionbare, AIDS 2001,15: 2196-8) and any mutation(s) in HLA-G untranslated region in DNA samples obtained from both Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote d'Ivoire and Perinatal AIDS Collaborative Transmission Study (PACTS), for possibly increase or decrease in the susceptibility of a neonate to HIV-1- perinatal transmission. Approach: DNA samples will be obtained from HIV-1-infected and uninfected mother-child pairs followed as part of Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote d'Ivoire and Perinatal AIDS Collaborative Transmission Study will be screened by the following techniques: WAVETM Nucleic Acid Fragment Analysis, allele-specific polymerase chain reaction (PCR), single strand conformational polymorphism (SSCP), followed by DNA cloning/sequencing. Molecular data from this study will be subjected to Fisher's exact test, Maximum likelihood, Linked disequilibrum parameter, Odd ratio, Relative risk analysis to groups value. Results will furnish new insights into the basic mechanisms of the viral pathogenesis in AIDS, especially the contribution of certain host genetic factors to HIV-1 perinatal infection.