THE BLOCKS TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT AND REV FUNCTIONS IN MOUSE-CELL LINES ARE INDEPENDENT

Rodent cells present two blocks precluding the expression of the human immunodeficiency virus type 1 (HIV-1) genome. First, the viral protein Tat is only poorly active in these cells. Second, when the HIV-1 provirus is integrated in the genome of mouse cells, it electively fails to express the viral structural proteins, indicating a block to Rev action. Both defects can be complemented by fusion of the infected mouse cells with uninfected human cells. Because the production of high levels of Rev is dependent on Tat-mediated transactivation and because both Tat and Rev bind the viral transcript, it has been hypothesized that the two blocks found in rodent cells might be linked. In the present work, we demonstrate that overexpression of Rev in mouse cell lines does not relieve their block in HIV-1 structural-gene expression. In addition, we show that this defect is also present in human-mouse cell hybrids which contain human chromosome 12 and support Tat function. On that basis, we conclude that the blocks to HIV-1 Tat and Rev action in mouse cell lines are independent and result from the absence of distinct cellular elements that are critical for HIV-1 gene expression.