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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
Author(s) -
BERG RANDI S.,
AGGERHOLM ANNI,
BERTELSEN LONE S.,
ØSTERGAARD LARS,
PALUDAN SØREN R.
Publication year - 2009
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2008.00024.x
Subject(s) - transactivation , interferon regulatory factors , biology , toll like receptor , p38 mitogen activated protein kinases , host factor , tlr4 , long terminal repeat , transcription factor , kinase , interferon , virology , mapk/erk pathway , microbiology and biotechnology , signal transduction , receptor , virus , innate immune system , gene , gene expression , genetics
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.