High and inducible expression of human immunodeficiency virus type 1 (HIV-1) Nef by adenovirus vector does not disturb potent antigen presentation by monocyte-derived dendritic cells

• Published in: Microbes and infection 2006-08, Vol.8 (9), p.2522-2530
• Main Authors: Yamamoto, Takuya, Isogai, Maya, Otake, Kaori, Tsunetsugu-Yokota, Yasuko
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus; Adenovirus vector; AIDS Vaccines - immunology; Antigen Presentation - immunology; Biological and medical sciences; CD4 Antigens - biosynthesis; CD4 Antigens - genetics; CD4-Positive T-Lymphocytes - immunology; Dendritic cells; Dendritic Cells - immunology; Down-Regulation; Fundamental and applied biological sciences. Psychology; Gene Products, nef - biosynthesis; Gene Products, nef - genetics; Gene Products, nef - immunology; Genes, nef; Genetic Vectors - genetics; HIV-1; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - metabolism; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Monocytes - immunology; Nef; nef Gene Products, Human Immunodeficiency Virus; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2006.07.002

Numerous studies indicated that Nef is a pleiotropic factor. Although it has been shown that Nef impairs the antigen-presenting activity of dendritic cells, more recent studies have shown no such impairment. This issue is critical for designing a vaccine expressing Nef. To refine our knowledge regarding the effect of Nef on dendritic cells, we developed constitutive and inducible adenovirus vector systems that express high levels of Nef in monocyte-derived dendritic cells (MDDCs). We showed here that Nef expression clearly downregulated CD4 expression of MDDCs but had little or no effect on other surface molecules, including MHC class I. Nef also did not affect the functional maturation of MDDCs. Use of the inducible Nef-expression system clearly revealed that adenovirus infection per se modulates cytokine secretion and the expression of apoptosis-related molecules in MDDCs, whereas Nef had no effect on these functions. Moreover, the antigen-presenting activity of MDDCs was not disturbed by the presence of Nef. On the contrary, we found that Nef-expressing MDDCs generated from HIV-1-infected individuals efficiently activated Nef-reactive T cells. Therefore, although adenovirus vector may modulate some aspects of MDDC function, Nef-expressing adenovirus would be served as one of HIV vaccine candidates.