NICHD Small Grants Programs

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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.