Speck
Fakultäten » Medizinische Fakultät » Infektionskrankheiten und Spitalhygiene, Klinik für » Prof. Dr. Rainer Weber » Speck
Completed research project
| Title / Titel | CD4 expression level on HIV target cells: A prognostic factor for disease progression? | ||
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| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | HIV infects cells via a receptor complex consisting of CD4 and one of the chemokine receptors CCR5 or CXCR4. CD4 must be expressed at sufficient density on the cell surface for HIV to efficiently enter the cells. However, once a cell is infected, viral gene products (e.g. Nef) downregulate CD4. This downmodulation of CD4 appears to confer a replicative advantage to HIV. Thus, we are confronted with two different requirements for an efficient HIV infection: 1.) high CD4 cell-surface levels for initial infection of cells, and 2.) low CD4 levels for spreading infection. In vivo, CD4 expression overall on CD4+ T-cells from HIV-infected subjects is significantly lower than in healthy individuals. Whereas acute SIV and HIV infection are accompanied by a marked depletion of CD4+ T-cells and massive infection of CD4+ T-cells occurs during acute SIV infection, the vast majority of cells (≥ 99%) from chronically HIV-infected patients are not infected. Thus, CD4 downmodulation is independent of productive HIV infection of the single cell; the mechanisms contributing to the overall lower expression level remain unknown. We would like to emphasize that we will focus on the chronic stage of HIV infection. We hypothesize that CD4 downmodulation predicts the course of HIV disease. Although considerable work has linked changes in levels of the chemokine coreceptors to disease progression, no definitive longitudinal study has yet examined the impact of CD4 expression level on disease progression rate. Moreover, it remains to be shown whether CD4 is also downregulated in other HIV target cells such as macrophages that have lower basal levels of CD4 than CD4+ T-cells, and to what extent this relates to HIV pathogenesis. |
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| Keywords / Suchbegriffe | HIV, chronic infection, CD4, CCR5, CXCR4, monocytes, lymphocytes | ||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
SNF (Programm NFP) Swiss HIV Cohort Study |
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| Duration of Project / Projektdauer | Jan 2007 to Dec 2008 |