Intracellular overexpression of HIV-1 Nef impairs differentiation and maturation of monocytic precursors towards dendritic cells.
Nef functions as an immunosuppressive factor critical for HIV-1 replication, survival and development of AIDS following HIV-1 infection. What effects Nef exerts on differentiation and maturation of monocytes towards dendritic cells (DCs) remains greatly controversial. In this study, we used THP-1 (human monocytic leukemia cell line) as monocytic DC precursors to investigate how overexpression of HIV-1 Nef influences the processes of differentiation and maturation of dendritic cells. In striking contrast to negative controls, our results showed that morphological and phenotypical changes (CD11c, CD14, CD40, CD80, CD83, CD86, and HLA-DR) occurred on recombinant THP-1 expressing HIV-1 Nef (short for Nef) upon co-stimulation of GM-CSF/IL-4 or GM-CSF/IL-4/TNF-α/ionomycin. Moreover, CD4, CCR5, and CXCR4 were also down-regulated on Nef. It might be hypothesized that Nef prevents superinfection and signal transduction in HIV-1 infected monocytes. Collectively, our study demonstrates that long-lasting expression of Nef at high levels indeed retards differentiation and maturation of dendritic cells in terms of phenotype and morphology. We are hopeful that potentially, stable expression of intracellular Nef in vivo may function as a subtle mode to support long-lasting HIV-1 existence.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China.
Yan
Y
Guo
Wen-Wen
WW
Xu
Jie
J
Song
Wen
W
Deng
Di-Qiu
DQ
Liu
Hua-Tang
HT
Zhang
D002454:Cell Differentiation; D045744:Cell Line, Tumor; D048430:Cell Shape; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D015536:Down-Regulation; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D011991:Receptors, Virus / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
D011991:Receptors, Virus; D011994:Recombinant Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus