Human immunodeficiency virus (HIV)-1 Tat downregulates the phosphorylation of recepteur d'origine nantais (RON) receptor tyrosine kinase induced by macrophage-stimulating protein

The aim of this study is to examine the effects of the human immunodeficiency virus (HIV)-1 Tat protein on the expression and phosphorylation of recepteur d'origine nantais (RON) receptor tyrosine kinase and the mechanisms involved. We first determined the expression levels of RON and macrophagestimulating protein (MSP) were determined in the peripheral blood of HIV-positive patients and control subjects. The 293T cells were transfected with the pDR2-RON plasmid to establish the 293T-RON cell line. The pcDNA3.1 (+)-Tat-His plasmid was constructed to obtain recombinant Tat protein. The 293T-RON cells pretreated with MSP were co-cultured with the H9/HTLV-IIIB cells or were stimulated with the Tat protein; then, the change of RON expression was determined. This study revealed higher expression of RON and relatively lower expression of MSP in HIV-infected patients than in the uninfected patients. We demonstrated that HIV-1 Tat down-regulated the expression and phosphorylation of RON in 293T-RON cells. Flow cytometry analysis of 293T-RON cells revealed that RON was expressed in 293T-RON cells. The 293T-RON cells co-cultured with the H9/HTLV-IIIB cells RON expression did not change significantly, while stimulation with 500 ng/ml Tat considerably decreased RON expression in 293T-RON cells. These findings imply that Tat may play a role in modulating the function of RON, which is activated by MSP; this may provide a permissive environment for both HIV and other opportunistic microbes.