Failure of TLR4-driven NF-kappa B activation to stimulate virus replication in models of HIV type 1 activation

AIDS Research and Human Retroviruses
Sushila K NordoneGregg A Dean

Abstract

The interaction of HIV-1 with Toll-like receptors (TLR) on host target cells is incompletely understood. Data from several in vivo and in vitro model systems suggest that TLR2, TLR4, and TLR9 remain functional and if stimulated, cause an upregulation of viral replication. In the present studies employing two different chronically HIV-1-infected cell lines and highly purified TLR agonists, we found ligation of TLR2 and TLR9, but not TLR4, resulted in significant upregulation of HIV-1 production. This result was not due to a lack of TLR4 expression or impaired NF-kappa B activation. Using HEK293 cells transfected with individual TLRs and an HIV-1 LTR reporter confirmed that TLR4 signaling does not directly activate the HIV-1 LTR. Finally, ultrapurified LPS did not enhance production of IL-1 beta or IL-6 in chronically infected U1 cells, whereas significant cytokine production was observed in uninfected U937 cells. These results confirm the biological activity of ultrapurified LPS and raise the possibility that TLR4 signaling pathways may be altered during chronic HIV-1 infection. Collectively, these studies suggest that although several TLR can upregulate NF-kappaB in HIV-1-infected cells, upregulation of NF-kappaB alone is insuf...Continue Reading

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Citations

Mar 17, 2011·AIDS Research and Human Retroviruses·Juan C HernándezSilvio Urcuqui-Inchima
Jan 28, 2012·AIDS Research and Human Retroviruses·Juan C HernándezSilvio Urcuqui-Inchima
Dec 12, 2012·American Journal of Respiratory Cell and Molecular Biology·Jingjing LiShila K Nordone
Jun 24, 2010·Retrovirology·Trine H MogensenSøren R Paludan
Jan 13, 2009·Cellular Microbiology·Yi-Ting TsaiChuan-Liang Kao
Mar 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erika Schlaepfer, Roberto F Speck
Nov 5, 2019·Frontiers in Immunology·Amanda B MacedoAlberto Bosque

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