In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat cysteine rich peptide increase CCR5 expression in human monocytes, and this activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5 expression in monocytes. These results provide insight into a new mechanism by which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.
Amino Acid Sequence ; Cells, Cultured ; Cysteine ; chemistry ; Dose-Response Relationship, Drug ; Extracellular Fluid ; chemistry ; Gene Expression Regulation ; drug effects ; physiology ; Gene Products, tat ; chemistry ; pharmacology ; Humans ; Molecular Sequence Data ; Monocytes ; drug effects ; metabolism ; Peptides ; chemistry

In our previous work we reported that HIV Tat and 6 cysteine rich peptides of Tat induce tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in human monocytes (Yang et al., 2003). Here our results showed that HIV Tat and Tat cysteine rich peptide increase CCR5 expression in human monocytes, and this activity is inhibited by rabbit anti-Tat. Boiled Tat does not increase CCR5 expression in monocytes. These results provide insight into a new mechanism by which HIV Tat plays a key role in the pathogenesis of HIV-1 infection.

OBJECTIVETo study the effects of HIV Tat protein on CCR5 expression of monocytes and HIV infection in monocytes.

METHODSMembrane expression of CCR5 on monocytes was analyzed by flow cytometry. Stimulated with HIV Tat protein, monocytes were infected with monocyte-tropic HIV(Ba-L) and HIV gag p24 level in the supernatant was measured by ELISA methods.

RESULTSHIV Tat protein increased CCR5 expression in human monocytes,which was inhibited by rabbit anti-Tat polyclonal antibody. Tat protein also increased p24 level after monocyte-tropic HIV-1(Ba-L) infected monocytes.

CONCLUSIONTat increases CCR5 expression and HIV-1 infection in monocytes, which indicates that HIV Tat might be a key protein in HIV-1 infection.

Flow Cytometry ; Gene Products, tat ; pharmacology ; HIV ; HIV Infections ; metabolism ; Humans ; Monocytes ; metabolism ; Receptors, CCR5 ; biosynthesis ; genetics ; tat Gene Products, Human Immunodeficiency Virus