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

Abstract

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 macrophage-stimulating 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.

Key words: Human immunodeficiency virus (HIV)-1, Tat, receptor tyrosine kinase, macrophage-stimulating protein, inflammation regulation.