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 ؋ 10 9 ͞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 G 0 to the late G 1 phase of the cell cycle.

Differential Requirement for p56lck in HIV-tat Versus TNF-Induced Cellular Responses: Effects on NF-κB, Activator Protein-1, c-Jun N-Terminal Kinase, and Apoptosis

“…This binding leads to the down-regulation of CD4 by HIV-nef (47). HIV-tat is a transcription factor required for HIV-1 replication (48). Although HIV-tat has been used to design therapeutics for AIDS patients (49), our results suggest that inhibitors of p56 lck enzyme may also have significant therapeutic potential.…”

HIV-1-based defective lentiviral vectors efficiently transduce human monocytes-derived macrophages and suppress replication of wild-type HIV-1

“…However, deletion of the tat gene from our vector would prevent detection of the GFP reporter gene, which is under the transcriptional control of the Tat-dependent HIV-1 long terminal repeat (LTR) [44]. Thus, we believe that the presence of Tat in the vector does not detract from the main conclusions of the present work, particularly since Tat has been described to enhance HIV-1 replication and cell killing, rather than protecting cells from viral infection [50][51][52]. Future studies will examine Tat-defective constructs using different reporter gene cassettes.…”

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection

“…In infected cells, Tat promotes viral replication or transactivates the replication of tat-defective or latent proviruses [11]. In uninfected cells, Tat can modulate cellular gene expression [3,12,13], up-regulate HIV co-receptors [14,15], and induce or inhibit apoptosis [16,17]. Early inhibition of Tat function should contribute to control of viral replication and slowing of AIDS progression.…”