Role of mitogen-activated protein kinases, nuclear factor-κB, and interferon regulatory factor 3 in Toll-like receptor 4-mediated activation of HIV long terminal repeat

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2009-02, Vol.117 (2), p.124-132
• Main Authors: BERG, RANDI S, AGGERHOLM, ANNI, BERTELSEN, LONE S, ØSTERGAARD, LARS, PALUDAN, SØREN R
• Format: Article
• Language: English
• Subjects: human immunodeficiency virus; Human immunodeficiency virus 1; nuclear factor κB; Toll-like receptors
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1600-0463.2008.00024.x

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-κB 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.