Transactivation of Naturally Occurring HIV-1 Long Terminal Repeats by the JNK Signaling Pathway

Chen, Peifeng; Flory, Egbert; Avots, Andris; Jordan, Bruce W.M.; Kirchhoff, Frank; Ludwig, Stephan; Rapp, Ulf R.

doi:10.1074/jbc.m001149200

Cited by 17 publications

(5 citation statements)

References 72 publications

(59 reference statements)

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“…They bind a palindromic DNA sequence known as the TPA-responsive elements (TRE) at positions -306 to -285 and -242 to -222 of the LTR [59] as well as at positions +95 and +160, downstream of the transcriptional start site [59,60,188,189]. The sequence of these sites has been shown to evolve in a manner that facilitates efficient cell type-specific binding of AP-1 [59,192]. AP-1 acts as either an activator or repressor of transcription, depending on the components of the dimer [191,193].…”

Section: Introductionmentioning

confidence: 99%

Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage

et al. 2009

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Human immunodeficiency virus type 1 (HIV-1) has been shown to replicate productively in cells of the monocyte-macrophage lineage, although replication occurs to a lesser extent than in infected T cells. As cells of the monocyte-macrophage lineage become differentiated and activated and subsequently travel to a variety of end organs, they become a source of infectious virus and secreted viral proteins and cellular products that likely initiate pathological consequences in a number of organ systems. During this process, alterations in a number of signaling pathways, including the level and functional properties of many cellular transcription factors, alter the course of HIV-1 long terminal repeat (LTR)-directed gene expression. This process ultimately results in events that contribute to the pathogenesis of HIV-1 infection. First, increased transcription leads to the upregulation of infectious virus production, and the increased production of viral proteins (gp120, Tat, Nef, and Vpr), which have additional activities as extracellular proteins. Increased viral production and the presence of toxic proteins lead to enhanced deregulation of cellular functions increasing the production of toxic cellular proteins and metabolites and the resulting organ-specific pathologic consequences such as neuroAIDS. This article reviews the structural and functional features of the cis-acting elements upstream and downstream of the transcriptional start site in the retroviral LTR. It also includes a discussion of the regulation of the retroviral LTR in the monocyte-macrophage lineage during virus infection of the bone marrow, the peripheral blood, the lymphoid tissues, and end organs such as the brain. The impact of genetic variation on LTR-directed transcription during the course of retrovirus disease is also reviewed.

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Section: Introductionmentioning

confidence: 99%

Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage

et al. 2009

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“…Interestingly, c-Fos, JunB and JunD (but not Fra-1) were shown to be recruited to the nuc-1 region (Fig. 7A, left panels), where they had been previously demonstrated to bind (or not to bind concerning Fra-1) in vitro to the AP-1 binding sites identified in the 5′LTR [40]. As a control, no binding of AP-1 family members was observed in the HIV-1 vpr gene region (see Fig.…”

Section: Resultsmentioning

confidence: 76%

The AP-1 Binding Sites Located in the pol Gene Intragenic Regulatory Region of HIV-1 Are Important for Viral Replication

et al. 2011

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Our laboratory has previously identified an important intragenic region in the human immunodeficiency virus type 1 (HIV-1) genome, whose complete functional unit is composed of the 5103 fragment, the DNaseI-hypersensitive site HS7 and the 5105 fragment. These fragments (5103 and 5105) both exhibit a phorbol 12-myristate 13-acetate (PMA)-inducible enhancer activity on the herpes simplex virus thymidine kinase promoter. Here, we characterized the three previously identified AP-1 binding sites of fragment 5103 by showing the PMA-inducible in vitro binding and in vivo recruitment of c-Fos, JunB and JunD to this fragment located at the end of the pol gene. Functional analyses demonstrated that the intragenic AP-1 binding sites are fully responsible for the PMA-dependent enhancer activity of fragment 5103. Moreover, infection of T-lymphoid Jurkat and promonocytic U937 cells with wild-type and mutant viruses demonstrated that mutations of the intragenic AP-1 sites individually or in combination altered HIV-1 replication. Importantly, mutations of the three intragenic AP-1 sites led to a decreased in vivo recruitment of RNA polymerase II to the viral promoter, strongly supporting that the deleterious effect of these mutations on viral replication occurs, at least partly, at the transcriptional level. Single-round infections of monocyte-derived macrophages confirmed the importance of intragenic AP-1 sites for HIV-1 infectivity.

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“…2). Furthermore, TPT treatment interfered with a number of pathways important for HIV replication, including T cell receptor, JNK, and GTPase signaling and regulation of actin cytoskeleton (32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%