A proteomics investigation of the HIV-1 infection in T-cells

Abstract

The defining feature of the acquired immune deficiency syndrome (AIDS) is the human immunodeficiency virus (HIV-1) infection of CD4+ T lymphocytes, compromising the immune system, and rendering the body defenseless from common opportunistic infections. Infections with HIV-1 (virus type 1) are associated with significant morbidity and mortality worldwide. Current therapies are partially effective and difficult to sustain due to toxicity and viral resistance. However, considerable progress has been made in the identification of cellular genes essential to pathogenesis and viral infection. This thesis is designed to take these studies to the level of proteomics by utilizing state-of-the-art technology to further investigate the HIV-1 infection on CD4+ T-cells.Classic proteomic methods including two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and liquid chromatography (LC) coupled with mass spectrometry (MS) provide the backbone of the research. Innovative techniques including capillary electrophoresis (CE) in various separation modes and single-cell analysis guides proteomics into the 21st century of bioanalytical science. Improvements to CE have also been discovered in a novel separation procedure involving fractionating LC in combination with 2D-CE to provide complete protein profiles of CD4+ T-cells.