title: Immune activation of human brain microvascular endothelial cells inhibits HIV replication in macrophages.
abstract: There is limited information about the role of blood-brain barrier (BBB) endothelial cells (ECs) in the central nervous system (CNS) and their innate immunity against HIV. We examined whether brain ECs can be immunologically activated to produce antiviral factors that inhibit HIV replication in macrophages. Human brain microvascular ECs expressed functional toll-like receptor 3 (TLR3) that could be activated by polyinosinic-polycytidylic acid (PolyI:C), resulting in the induction of endogenous interferon-β (IFN-β) and IFN-λ. The TLR3 activation of ECs also induced the phosphorylation of interferon regulatory transcription factor 3 (IRF3) and IRF7, the key regulators of IFN signaling pathway. When supernatant (SN) of PolyI:C-activated EC cultures was applied to infected macrophage cultures, HIV replication was significantly suppressed. This SN action of ECs on HIV was mediated through both IFN-β and IFN-λ because antibodies to their receptors could neutralize the SN-mediated anti-HIV effect. The role of IFNs in EC-mediated anti-HIV activity is further supported by the observation that treatment with SN from EC cultures induced the expression of IFN-stimulated genes (ISGs: ISG56, OAS-1, and MxA) in macrophages. These observations indicate that brain microvascular ECs may be a key regulatory bystander, playing a crucial role in the BBB innate immunity against HIV infection.
authors: Animal Biosafety Level 3 Laboratory, School of Medicine, Wuhan University, Wuhan, People's Republic of China.
authors: Jieliang
authors: J
authors: Li
authors: Yizhong
authors: Y
authors: Wang
authors: Xu
authors: X
authors: Wang
authors: Li
authors: L
authors: Ye
authors: Yu
authors: Y
authors: Zhou
authors: Yuri
authors: Y
authors: Persidsky
authors: Wenzhe
authors: W
authors: Ho
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000276:immunology; D001812:Blood-Brain Barrier / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000276:immunology; D002467:Cell Nucleus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000276:immunology / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D008856:Microscopy, Fluorescence; D018448:Models, Immunological; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D034622:RNA Interference; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*
chemical_list: D017077:Culture Media, Conditioned; C494232:IRF3 protein, human; C494234:IRF7 protein, human; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D011971:Receptors, Immunologic; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D007371:Interferon-gamma; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C
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