title: Role of mitogen-activated protein kinases, nuclear factor-kappaB, and interferon regulatory factor 3 in Toll-like receptor 4-mediated activation of HIV long terminal repeat.
abstract: Monocytes/macrophages are known to represent a potential reservoir of human immunodeficiency virus type 1 (HIV-1), which ensures continuous replication of the virus in patients on highly active antiretroviral therapy (HAART). Infected macrophages are a highly productive source of HIV-1 during infections with common opportunistic pathogens. Previous studies report that toll like receptors (TLR)s play a role in HIV-1 replication in macrophages. Here, we investigate the three main pathways activated through TLR4 and the interactions with the HIV-1 long terminal repeat (LTR), using human embryonic kidney (HEK) 293 cells expressing TLR4 and transfected with a luciferase reporter under the control of the HIV-1 LTR. Here, we demonstrate, that TLR4-mediated activation of HIV-LTR is largely governed by the nuclear factor-kappaB pathway. Neither of the mitogen-activated protein kinases ERK1/2, JNK, or p38 nor the transcription factor interferon regulatory factor 3 were involved in the direct transactivation of HIV-LTR through stimulation of TLR4.
authors.affiliation: Department of Infectious Diseases, Skejby Hospital, Aarhus, Denmark.
authors.forename: Randi S
authors.initials: RS
authors.lastname: Berg
authors.forename: Anni
authors.initials: A
authors.lastname: Aggerholm
authors.forename: Lone S
authors.initials: LS
authors.lastname: Bertelsen
authors.forename: Lars
authors.initials: L
authors.lastname: Østergaard
authors.forename: Søren R
authors.initials: SR
authors.lastname: Paludan
mesh_terms: D002460:Cell Line; D016325:HIV Long Terminal Repeat; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases