HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages.
Immature dendritic cells are among the first cells infected by retroviruses after mucosal exposure. We explored the effects of human immunodeficiency virus-1 (HIV-1) and its Tat transactivator on these primary antigen-presenting cells using DNA microarray analysis and functional assays. We found that HIV-1 infection or Tat expression induces interferon (IFN)-responsive gene expression in immature human dendritic cells without inducing maturation. Among the induced gene products are chemokines that recruit activated T cells and macrophages, the ultimate target cells for the virus. Dendritic cells in the lymph nodes of macaques infected with simian immunodeficiency virus (SIV) have elevated levels of monocyte chemoattractant protein 2 (MCP-2), demonstrating that chemokine induction also occurs during retroviral infection in vivo. These results show that HIV-1 Tat reprograms host dendritic cell gene expression to facilitate expansion of HIV-1 infection.
Izmailova
Elena
E
Department of Medicine, Children's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
Bertley
Frederic M N
FM
Huang
Qian
Q
Makori
Norbert
N
Miller
Christopher J
CJ
Young
Richard A
RA
Aldovini
Anna
A
D000818:Animals; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015696:Gene Products, tat / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000502:physiology; D008213:Lymphocyte Activation; D008251:Macaca; D008264:Macrophages / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D007372:Interferons