Pathobiology of HIV in the Human Monocyte-Macrophage
Abstract
We have studied various aspects of HIV biology within the monocyte- macrophage. These studies included interactions of newly discovered cytokines in promoting monocytic cell development in the context of HIV infection. Both interleukin-3 and kit ligand/stem cell factor were found to augment myelopoiesis in vitro and protect monocyte-macrophage from toxic effects of Zidovudine and ganciclovir. Kit ligand/stem cell factor had no upregulatory effect on HIV transcription while interleukin-3 did. These studies set the stage for the use of these cytokines to reduce the cytotoxicity of important agents such as Zidovudine and ganciclovir in the treatment of HIV disease and its complicating opportunistic infections. We also discovered that the long-terminal repeat (LTR) of HIV contains motifs responsive to steroid hormone receptors. There appears to be a complex interplay among these transcription factors in terms of modulating virus expression in the monocyte-macrophages. These studies open a new avenue of research with regard to therapeutics based on retinoic acids. Efforts were initiated to introduce synthetic genes capable of inhibiting HIV into the monocyte-macrophages in novel adenoassociated virus (AAV) vectors. We have successfully constructed prototype vectors using the AAV backbone and found a high transduction efficiency in macrophages. Future studies Will examine the optimal constructs to inhibit HIV replication in these cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 10, 1993
- Accession Number
- ADA274745
Entities
People
- Jerome E. Groopman
Organizations
- Beth Israel Deaconess Medical Center