Tat Protein Induces Self-Perpetuating Permissivity for Productive HIV-1 Infection
Abstract
We report that human immunodeficiency virus type 1 (HIV-1) has evolved a self-perpetuating mechanism to actively generate cells permissive for productive and cytopathic infection. Only activated T cells can be productively infected, which leads to their rapid depletion (2 × 109/day in an infected individual). Establishment of productive HIV-1 infection 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 HIV-1 infection. Activation of primary T cells by Tat protein involved integrin receptors and was associated with activation of mitogen-activated protein kinases, including ERK1 and JNK kinase. Accordingly, these primary T cells progressed from G0 to the late G1 phase of the cell cycle.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- July 1997
- DOI:
- 10.1073/pnas.94.15.8116
- Bibcode:
- 1997PNAS...94.8116L