title: Modulation of intracellular restriction factors contributes to methamphetamine-mediated enhancement of acquired immune deficiency syndrome virus infection of macrophages.
abstract: Epidemiological studies have demonstrated that the use of methamphetamine (METH), a sympathomimetic stimulant, is particularly common among patients infected with HIV. In vitro studies have determined that METH enhances HIV infection of CD4+ T cells, monocyte-derived dendritic cells, and macrophages. In addition, animal studies have also showed that METH treatment increases brain viral load of SIV-infected monkeys and promotes HIV replication and viremia in HIV/hu-CycT1 transgenic mice. However, the mechanisms (s) of METH actions on HIV remain to be determined. In this study, we investigated the impact of METH on intracellular restriction factors against HIV and SIV. We demonstrated that METH treatment of human blood mononuclear phagocytes significantly affected the expression of anti-HIV microRNAs and several key elements (RIG-I, IRF-3/5, SOCS-2, 3 and PIAS-1, 3, X, Y) in the type I IFN pathway. The suppression of these innate restriction factors was associated with a reduced production of type I IFNs and the enhancement of HIV or SIV infection of macrophages. These findings indicate that METH use impairs intracellular innate antiviral mechanism(s) in macrophages, contributing to cell susceptibility to the acquired immune deficiency syndrome (AIDS) virus infection.
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.  wenzheho@temple.edu.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Jieliang
authors.initials: J
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Sinem
authors.initials: S
authors.lastname: Sakarcan
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology; D000818:Animals; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007372:Interferons / Q000037:antagonists & inhibitors / Q000378:metabolism; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D008694:Methamphetamine / Q000009:adverse effects* / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*; D015819:Substance Abuse, Intravenous; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D007372:Interferons