TAR LOOP-DEPENDENT HUMAN-IMMUNODEFICIENCY-VIRUS TRANSACTIVATION REQUIRES FACTORS ENCODED ON HUMAN CHROMOSOME-12

The trans-activator response region (TAR) RNA in the human immunodefic iency virus type 1 (HIV-1) and HIV-2 long terminal repeat forms stem-l oop secondary structures in which the loop sequence is essential for t rans activation. We investigated how the HIV trans-activation mechanis m encoded on human chromosome 12 relates to the TAR RNA loop-dependent pathway. DNA transfection experiments showed that trans activation in human-hamster hybrid cells with the single human chromosome 12 and hu man T-cell lines was highly dependent on the native sequences of the H IV-1 TAR loop and the HIV-2 5' TAR loop. In nonhuman cell lines or hyb rid cells without chromosome 12 that supported trans activation, the c ellular mechanism was independent of the HIV-1 TAR loop and the respon se to mutations in the HIV-2 TAR loops differed from that found in hum an T-cell lines and human-hamster hybrid cells with chromosome 12. Our results suggest that the human chromosome 12 mechanism interacts dire ctly with the TAR RNA loop or indirectly by regulating TAR RNA-binding proteins.