Lipopolysaccharide suppresses HIV-1 replication in human monocytes by protein kinase C-dependent heme oxygenase-1 induction.
LPS is an important component of the Gram-negative bacteria cell wall. It activates monocytes and induces multiple host immune and inflammatory responses. Interestingly, in spite of inducing host-inflammatory responses, LPS also protects monocyte-derived macrophages from infection by HIV-1. In this report, we have shown that LPS treatment of human monocyte-derived macrophages markedly suppressed HIV-1 replication, even on addition to infected cells 24 h after infection. Inhibition of HIV-1 replication was associated with PKC-dependent induction of HO-1, a cytoprotective enzyme known to catabolize heme. Pretreatment with the PKC inhibitor Go 6976 not only substantially inhibited LPS-mediated induction of HO-1 but also attenuated LPS-induced suppression of HIV replication. Significant reduction of HIV replication by inhibitors of JNK, NF-kappaB, and PI3K was independent of a LPS-mediated anti-HIV effect. Specificity of HO-1 was confirmed by substantial reversal of LPS-induced viral replication by pretreatment of cells with SnPP IX, an inhibitor of HO-1 enzyme activity. These results demonstrate a previously undefined function of HO-1 as a host defense mechanism in LPS-mediated inhibition of HIV-1 replication.
Devadas
Krishnakumar
K
Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike (HFM-315), Rockville, MD 20852-1448, USA.
Hewlett
Indira K
IK
Dhawan
Subhash
S
D004791:Enzyme Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D009000:Monocytes / Q000201:enzymology* / Q000821:virology; D011493:Protein Kinase C / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D051547:Heme Oxygenase-1; D011493:Protein Kinase C