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Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
Surface CD4 expression modulated by a cellular factor induced by HIV type 1 infection
Dennis Sheeter1, Pinyi Du, Steffney Rought
1Department of Medicine, University of California San Diego, La Jolla, California 92093-0679, USA.
Insights
Human immunodeficiency virus type 1 (HIV-1) infection alters host gene expression. This study found that nuclear factor I-B2 (NFI-B2) impairs CD4 transcription, reducing HIV-1 production.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infection leads to cellular dysfunction by altering host gene expression.
- Understanding host-pathogen interactions is crucial for developing therapeutic strategies against HIV-1.
Purpose of the Study:
- To investigate the role of host cell gene modulation during HIV-1 infection.
- To elucidate the specific function of nuclear factor I-B2 (NFI-B2) in HIV-1 pathogenesis.
Main Methods:
- Utilized high-density oligonucleotide microarray technology to identify modulated host genes in HIV-1 infected cells.
- Generated a Jurkat T cell line with constitutive NFI-B2 expression for functional studies.
- Analyzed viral production, surface CD4 expression, and CD4 mRNA levels.
Main Results:
- HIV-1 infection modulated several host cell genes, including NFI-B2.
- Constitutive NFI-B2 expression in Jurkat T cells reduced HIV-1 production.
- NFI-B2 expression led to downregulation of surface CD4 and CD4 mRNA, indicating impaired CD4 transcription.
- CXCR4 coreceptor expression remained unchanged.
Conclusions:
- NFI-B2 plays a significant role in modulating CD4 expression during HIV-1 infection.
- HIV-1-induced modulation of NFI-B2 may contribute to the reduction of cell surface CD4 expression.
- NFI-B2 represents a potential target for therapeutic intervention in HIV-1 infection.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) alters gene expression in infected cells, leading to cellular dysfunction. We uncovered a number of host cell genes that are modulated in both CD4(+) T cell lines and primary CD4(+) T lymphocytes infected with HIV-1, using high-density oligonucleotide probe microarray technology. We focused on one gene in particular, nuclear factor I-B2 (NFI-B2), because of its high level of expression. NFI-B2 is a member of the nuclear factor I family of nuclear proteins, which are known to be involved in viral and cellular transcription. To better understand the role of NFI-B2 during HIV-1 infection, we generated a Jurkat T cell line that constitutively expressed NFI-B2. After infection with HIV-1, these cells produced fewer viruses because of a downregulation of surface CD4 expression. The surface expression of the coreceptor, CXCR4, remained unchanged. Furthermore, levels of CD4 mRNA were reduced in NFI-B2-producing cells, suggesting that expression of NFI-B2 impairs CD4 transcription. Modulation of NFI-B2 by HIV-1 may represent yet another mechanism by which HIV infection reduces cell surface expression of CD4.
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