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Updated: Aug 5, 2026
Lentivirus Production
Published on: October 2, 2009
Lentivirus infection of macrophages
J E Clements1, M C Zink, O Narayan
1Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract:
The ovine and caprine lentiviruses infect monocytes, and the viral DNA is integrated into the cellular DNA. The provirus remains silent until the monocyte matures into a macrophage. Intrinsic to this maturation is the induction of a class of immediate early genes in the monocyte that includes the transcription factors JUN and FOS. These transcription factors are thought to couple short-term signals in the cell to long-term cellular differentiation by regulation of specific cellular genes. Thus, JUN and FOS bind to the AP-1 site in the promoters of cellular genes and activate their transcription, resulting in maturation of the monocyte into a macrophage. In addition, these cellular factors activate the same AP-1 sequence in the visna virus LTR, leading to transcriptional activation, full viral gene expression, and production of progeny virus. The expression of viral antigens in the context of MHC class II on the macrophage leads to the production of cytokines and a lymphoproliferative response that causes the lesions in specific target organs in an infected animal. We still understand only the framework of these events. The specific mechanisms by which viral genes alter macrophage gene expression and the molecular basis of different viral tropism for specific tissue macrophages, i.e. microglia, remain to be determined.
Insights
Ovine and caprine lentiviruses hijack monocyte-to-macrophage differentiation by activating viral gene expression through transcription factors JUN and FOS. This leads to immune responses and disease lesions in infected animals.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Ovine and caprine lentiviruses infect monocytes, integrating viral DNA that remains latent until monocyte maturation.
- Monocyte differentiation into macrophages involves immediate-early genes, including transcription factors JUN and FOS.
Purpose of the Study:
- To elucidate the mechanism by which lentiviruses exploit host cell machinery for viral replication.
- To understand how viral gene expression is regulated during macrophage differentiation.
Main Methods:
- The study focuses on the molecular interactions between viral DNA, host transcription factors (JUN, FOS), and the viral LTR (Long Terminal Repeat).
- Analysis of AP-1 site activation in both cellular genes and the visna virus LTR.
Main Results:
- Transcription factors JUN and FOS, crucial for monocyte maturation, bind to the AP-1 site in cellular genes and the visna virus LTR.
- Activation of the AP-1 site in the viral LTR leads to transcriptional activation, viral gene expression, and progeny virus production.
- Expression of viral antigens on macrophages triggers cytokine production and lymphoproliferative responses, causing organ lesions.
Conclusions:
- Lentiviruses utilize host transcription factors (JUN, FOS) to induce viral replication during macrophage differentiation.
- Further research is needed to determine the precise mechanisms of viral gene alteration of macrophage expression and tissue tropism.
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