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Effects of CD45 on NF-kappa B. Implications for replication of HIV-1
A Baur1, S Garber, B M Peterlin
1Howard Hughes Medical Institute, University of California at San Francisco 94143-0724.
Insights
CD45 protein regulates T cell activation and HIV-1 replication. Blocking CD45 reduces HIV-1 gene expression, while its absence enhances viral replication by increasing NF-kappa B activity.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- T cell activation via the T cell receptor (TCR) increases human immunodeficiency virus type 1 (HIV-1) replication.
- Anti-CD45 antibodies have been observed to inhibit these activation-induced effects in HIV-1-infected individuals.
Purpose of the Study:
- To investigate the relationship between CD45 and HIV-1 replication.
- To determine the effect of CD45 modulation on HIV-1 gene expression and viral replication.
Main Methods:
- Measuring HIV-1 long terminal repeat (LTR) expression in T cell lines stimulated with anti-CD45 antibodies.
- Analyzing T cell lines lacking CD45 expression.
- Assessing NF-kappa B complex activity in the nucleus.
Main Results:
- Anti-CD45 antibodies decreased activated, but not basal, HIV-1 LTR expression.
- T cells lacking CD45 showed increased viral replication and gene expression due to nuclear NF-kappa B.
- HIV-1-infected T cells exhibited reduced surface CD45 levels.
Conclusions:
- CD45 plays a significant role in T cell physiology and HIV-1 replication.
- Modulation of CD45 affects HIV-1 gene expression and viral load.
Abstract:
Increased levels of replication of the HIV type 1 are observed after the activation of infected T cells through the TCR. However, anti-CD45 antibodies inhibit these effects in cells from infected individuals. In this study, we examined interrelationships between CD45 and HIV-1 further. We measured effects on the HIV-1 LTR in T cell lines that were stimulated with antibodies against CD45 and in those that lacked the expression of CD45 on their surfaces. First, anti-CD45 antibodies did not affect basal but decreased activated levels of expression from the HIV-1 LTR. Second, T cells, which lack CD45 and cannot signal via the TCR, supported higher levels of viral replication and gene expression. This was due to the presence of active NF-kappa B complexes in the nucleus of CD45- T cells. Additionally, infected T cells displayed lower levels of CD45 on their surfaces. Thus, CD45 plays an active role in the physiology of T cells and in the replication of HIV-1.