Identification and characterization of differentially expressed mRNAs in HIV type 1-infected human T cells

We used a novel differential display (DD) technique to identify host factor s involved in virus replication, pathogenesis, and host response in HIV-1-i nfected T cells. Thirteen cDNA fragments differentially expressed in HIV-1( NL4-3)-infected MT-4 cells prior to the occurrence of specific apoptotic ce ll death were sequenced and identified. Two of seven elevated genes were id entical to HIV-1 sequences and the other five were MIP-1 alpha, ACTE-III, C D11c, arginase I, and CCR5. The six downregulated genes included prothymosi n-alpha, Jaw-1, proteasome subunit XAPC7, splicing factor 9G8, GA17 protein , and an unknown mRNA. Northern blot and RT-PCR analyses confirmed the alte red gene expressions in MT-4 cells as well as in another T cell line, MOLT- 4. We also revealed that the amount of MIP-1 alpha in culture supernatant o f HIV-1-infected cells was increased by more than 15-fold relative to contr ol cells, and the expression of its receptor CCR5 was cooperatively upregul ated on the surface of these cells. Furthermore, the upregulation of CD11c after HIV-1 infection was slightly inhibited by blocking the MIP-1 alpha-me diated signal transduction. These results indicate that genes altered on HI V-1 infection may be mutually organized and play an important role in HIV-1 -induced pathogenesis.