Viral infections in immunocompromised hosts
Thursday 5 March 2009
Dr. Debbie van Baarle
Project
HIV-infected individuals are of risk to develop virus-related diseases after reactivation of persistent viruses like EBV and CMV. Both viral kinetics as well as specific cellular immunity to these common herpesviruses are studied in both children and adults within the clinical viro-immunology section of the department of Immunology.
EBV viral load is increased in immunocompromised patients. This is a reflection of reactivation due to reduced immunity and predictive of development of Post-transplant lymphoproliferative disease after (bone marrow) transplantation. However, in HIV-infection increased EBV load is a reflection of an altered viral setpoint after acute HIV-infection and is not predictive of lymphoma development. Our studies indicate that immune activation may play a role and therefore we will analyse whether induced immune activation by a vaccine will lead to an altered EBV-setpoint.
As viral infections in HIV-positive children are hardly investigated, we have initiated studies on the presence of infections as well as specific immunity to these infections in HIV+ children, who are mostly treated with HAART. Interestingly, EBV load in these children is also increased and
in this case not only B cells, but also CD4+ and CD8+ T cells are infected by the virus. Therefore, increased EBV load in adults may also be caused by this altered biology of EBV-infection and we will investigate whether this is the case.
Techniques
Cell separation techniques, Q-PCR, culure, FACS-analysis, elispot-assay
Duration
6 or 9 months
Contact
Dr. Debbie van Baarle, d.vanbaarle@umcutrecht.nl, 088 755 539 46
Dr. Kristin Denzer, k.denzer@umcutrecht.nl, 088 75 576 73
More info
Website UMC Utrecht - Dept. of Immunology
Key Publications
D. van Baarle et al. Dysfunctional Epstein-Barr virus (EBV)-specific CD8+ T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin’s Lymphoma. Blood 98, 2001: 146-155
D. van Baarle et al. Failing immune control due to impaired CD8+ T cell maturation: CD27 may provide a clue. Trends Immunol 23, 2002: 586-591
E. Piriou et al. Novel method for detection of virus-specific CD4(+) T cells indicates a decreased EBV-specific CD4(+) T cell response in untreated HIV-infected subjects. Eur. J. Immunol. 35, 2005: 796-805
E. Piriou et al. Reconstitution of Epstein-Barr virus latent but not lytic antigen-specific CD4+ and CD8+ T cells after HIV treatment with highly active antiretroviral therapy. J. Immunol. 2005: Aug 1;175(3):2010-2017
E. Piriou et al. Loss of EBNA1-specific memory CD4+ and CD8+ T cells in HIV-infected patients progressing to AIDS-related non-Hodgkin Lymphoma. Blood 2005; in press
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