Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages

• Published in: Biochemical and biophysical research communications 2013-06, Vol.435 (3), p.373-377
• Main Authors: Zhou, Zhao-Hua, Kumari, Namita, Nekhai, Sergei, Clouse, Kathleen A., Wahl, Larry M., Yamada, Kenneth M., Dhawan, Subhash
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Adaptor Proteins, Signal Transducing - biosynthesis; AIDS VIRUS; CCR-5; Chemokines; Chemokines - biosynthesis; Chemokines - metabolism; ENZYMES; HEME; Heme oxygenase-1; Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - physiology; HIV Infections - enzymology; HIV Infections - immunology; HIV Infections - prevention & control; HIV-1; HIV-1 - immunology; HIV-1 - pathogenicity; Host-Pathogen Interactions - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; INFLAMMATION; INHIBITION; Lipopolysaccharides - pharmacology; Macrophage Activation - immunology; MACROPHAGES; Macrophages - enzymology; Macrophages - immunology; Macrophages - virology; MONOCYTES; RECEPTORS; Receptors, Chemokine - antagonists & inhibitors; SECRETION; TRANSMISSION ELECTRON MICROSCOPY
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.04.095

•Lipopolysaccharide stimulation of heme oxygenase-1 (HO-1) ameliorated HIV-1 infection of primary human macrophages.•The partial protection by HO-1 against HIV infection was associated with induction of chemokines such as MIP1α and MIP1β.•This mechanism explains lipopolysaccharide-stimulated HO-1-mediated inhibition of HIV-1 infection of macrophages. We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy. LPS activation of MDM markedly enhanced the expression of heme oxygenase-1 (HO-1), a potent inducible cytoprotective enzyme. Increased HO-1 expression was accompanied by elevated production of macrophage inflammatory chemokines (MIP1α and MIP1β) by LPS-activated MDM, significantly decreased surface chemokine receptor-5 (CCR-5) expression, and substantially reduced virus replication. Treatment of cells with HO-1 inhibitor SnPP IX (tin protoporphyrin IX) attenuated the LPS-mediated responses, HIV-1 replication and secretion of MIP1α, MIP1β, and LD78β chemokines with little change in surface CCR-5 expression. These results identify a novel role for HO-1 in the modulation of host immune response against HIV infection of MDM.