Voelcker Academy

Research Symposium 2009

 

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Elizabeth Santiago

Role of Epigenetics in the Regulation of CCR5, the Major HIV-1 Coreceptor

Elizabeth Santiago

Mentor(s): Camille Ratliff, Nicky Chopra, Germán Gornalusse, Dr. Srinivas Mummidi and Dr. Sunil Ahuja

Over 38 million adults are infected with the Human Immunodeficiency Virus Type 1 (HIV-1). However, not all those exposed to the virus become infected, and for those infected, the time of progression to AIDS and death varies dramatically. This inter-individual variation is caused by a combination of environmental, viral, and host factors that collectively influence the host response to HIV-1. Over the last decade, understanding the genetic determinants of the host response has been one of the major areas of investigations of AIDS researchers. This can not only provide important clues regarding the determinants of HIV-1 pathogenesis, but also provide targets for drug development. Epigenetics regulates various genomic functions that are controlled by heritable but potentially reversible changes in DNA methylation and/or chromatin structure, without a change to the actual sequence of DNA. The initial entry of HIV-1 into a cell requires the expression of two receptors on the cell surface, CD4 and CC chemokine receptor 5 (CCR5). It has been demonstrated that the level of CCR5 expressed on the cell surface correlates with the relative ease with which HIV-1 may infect a cell in vitro. Delineating the molecular mechanisms that control the expression of CCR5 is of importance to our understanding of HIV-1 pathogenesis.

The purpose of this experiment was to answer the following questions:

  • Does DNA methylation play a role in CCR5?
  • Does memory T cell commitment involve CCR5 demethylation?

The latter question was raised because CCR5 expression is mainly found on memory T cell subsets.