TAT PROTEIN INDUCES SELF-PERPETUATING PERMISSIVITY FOR PRODUCTIVE HIV-1 INFECTION

We report that human immunodeficiency virus type I (HIV-1) has evolved a self-perpetuating mechanism to actively generate cells permissive f or productive and cytopathic infection, Only activated T cells can be productively infected, which leads to their rapid depletion (2 x 10(9) /day in an infected individual), Establishment of productive HIV-1 inf ection therefore requires continual activations from the large pool of quiescent T cells, Tat protein, which is secreted by infected cells, activated uninfected quiescent T cells in vitro and in vivo. These Tat -activated uninfected cells became highly permissive for productive HI V-1 infection, Activation of primary T cells by Tat protein involved i ntegrin receptors and was associated with activation of mitogen-activa ted protein kinases, including ERK1 and JNK kinase, Accordingly, these primary T cells progressed from G(0) to the late G(1) phase of the ce ll cycle.