Journal article
IL-1beta-induced differentiation of a human bone marrow promonocytic progenitor cell line and susceptibility to HIV-1
Journal of neurovirology, Vol.13, pp.62-62
01 Jan 2007
Abstract
The role of the bone marrow compartment in the pathologic events associated with AIDS and HIV-1 dementia (HIVD) has not been elucidated. Interestingly, CD34+/CD38- progenitor cells within the bone marrow are refractile to HIV-1 infection, possibly due to their low level expression of HIV-1 co-receptors, CXCR4 and CCR5, which upon differentiation are upregulated, potentially increasing susceptibility to infection. The CD34+/CD38+ TF-1 bone marrow progenitor cell line was selected as a model to study HIV-1 infection during the differentiation process of hematopoietic progenitor cells. TF-1 cells were treated with a number of metabolic activators including PMA, conditioned media from PMA-treated cells, as well as cytokines such as GM-CSF, M-CSF, IL-1beta, TNF-alpha, IL-4 and their maturation was monitored through surface marker expression by flow cytometry. Interestingly, IL-1beta, alone or in combination with TNF-alpha leads to CXCR4 and CCR5 upregulation and preservation of CD4 expression while differentiating TF-1 cells, thereby providing a window of opportunity for HIV-1 infection to occur. Moreover, transient and stable transfection analysis demonstrated that the HIV-1 LTR activity was significantly increased following treatment of TF-1 cells with IL-1beta and conditioned media. Importantly, IL-beta treatment led to a large increase in p24 production in TF-1 cells infected with the CCR5 using virus BaL and to a modest increase in cells infected with the CXCR4 using virus IIIB. These results indicate that progenitor cell differentiation leads to upregulation of HIV-1 co-receptor expression and enhancement of the LTR activity, contributing to increased HIV-1 susceptibility and productive replication.
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Details
- Title
- IL-1beta-induced differentiation of a human bone marrow promonocytic progenitor cell line and susceptibility to HIV-1
- Creators
- A AlexakiS PassicM NonnemacherE KilareskiB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.13, pp.62-62
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170501804721