Title:Modulation of Intracellular Restriction Factors Contributes to Methamphetamine- Mediated Enhancement of Acquired Immune Deficiency Syndrome Virus Infection of Macrophages
Volume: 10
Issue: 5
Author(s): Xu Wang, Yizhong Wang, Li Ye, Jieliang Li, Yu Zhou, Sinem Sakarcan and Wenzhe Ho
Affiliation:
Keywords:
HIV, Interferon, Intracellular restriction factors, Macrophages, METH, microRNAs, SIV, Interferon regulatory
factor, Interferon regulatory, IFN, JAK-STAT.
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.