Human immunodeficiency virus type 1 (HIV-1) infection and expression in intestinal epithelial cells: Role of protein kinase A and C pathways in HIV-1transcription

Human immunodeficiency virus (HIV) can infect human colon epithelial cell l ines by both CD4-dependent and -independent mechanisms. The present studies assessed cellular factors that are important for HIV-1 transcription in hu man colon epithelial cells. The HIV-1 long terminal repeat (LTR) was shown to contain functional DNA cis-regulatory elements downstream of the viral t ransactivator-responsive element in the transcribed noncoding 5' leader seq uence, These downstream regulatory elements, termed DSE, can bind c-Fos and JunD and transmit protein kinase C activation signals to the HIV LTR. More over, specific Jun and Fos transcription factors can transactivate HIV-1 pr ovirus in human colon epithelial cells. The DSE also bind related proteins of the CREB/ATF family. Ln this regard, the DSE behave as 12-0-tetradecanoy lphorbol 13-acetate responder element-like cAMP-responsive elements because they bind both AP-1 and CREB/ATF transcription factors, thereby permitting induction of the HIV-1 LTR by both protein kinase C and A activation signa ls.