The functional consequences of delivery of HIV-1 Nef to dendritic cells using an adenoviral vector.
The Nef gene is a major determinant of HIV-1 pathogenicity. Several immunomodulatory functions have been reported for Nef, including down-regulation of CD4 and class I MHC in T-lymphocytes, and the ability to enhance viral transmission from macrophages and dendritic cells (DC) to T-lymphocytes. In this study, HIV-1 (SF2 strain) Nef was expressed in human monocyte-derived dendritic cells, using an adenovirus based delivery system. Nef expression resulted in decreased CD4 levels, but no change to class I MHC, and no impairment in the ability of DC to stimulate recall PPD responses, mixed leukocyte responses, or hepatitis B-specific CD8 responses. The adenovirus vector itself stimulated a strong recall CD4 response in all individuals tested, and also induced up-regulation of class I MHC, CD86 and CD40 on the dendritic cell surface. The study provides no evidence that HIV Nef impairs the function of human dendritic cells, and suggests that delivery of Nef to dendritic cells may be one strategy with which to stimulate an HIV-1 immune response.
Maccormac
Luci P
LP
Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, W1T 4JF London, UK.
Jacque
Jean Marc
JM
Chain
Benjamin
B
D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D054407:Chemokine CCL4; D003713:Dendritic Cells / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005814:Genes, Viral / Q000235:genetics*; D015754:Genes, nef / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics
D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins