HLA-G Regulatory Variant Assessment in HIV-1 Perinatal Transmission (pilot)

Morehouse School Of Medicine, Atlanta GA

Investigators

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Abstract

DESCRIPTION (provided by applicant): Perinatal transmission accounts for more than 90 percent of HIV-infection in children. A thorough understanding of the molecular and genetic mechanisms of the host immune gene response (such as chemokines, cytokines, and HLA polymorphisms) effecting the pathogens and transmission consequences of host-HIV-I 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 a non-classical class I MHC gene and it is highly expressed in extravillous cytotrophoblast at the maternal-fetal interface. Specific aim: To examine the potential role(s) played by the 5. regulatory region of the HLA-G gene variant(s) which may affect the binding of transcription factors, possibly increasing or decreasing the susceptibility of a neonate to HIV perinatal infection. Approach: DNA samples already obtained from HIV-1-infected and uninfected mother-child pairs followed as part of 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 disequilibrium parameter, odd ratio, relative risk analyses 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. The identification of predicators of HIV-l perinatal transmission would represent a major improvement and allow more precise counseling of pregnant women.