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Leukemia Inhibitor Factor (LIF) Inhibits HIV-1 Replication Via Restriction of Stat 3 Activation.
- Source :
- AIDS Research & Human Retroviruses; Mar2007, Vol. 23 Issue 3, p398-406, 9p
- Publication Year :
- 2007
-
Abstract
- Leukemia inhibitor factor (LIF) has been shown to potently inhibit HIV-1 replication in vitroand in human organ explant cultures. Furthermore, LIF activates the JakStat signaling pathway with which many viruses, including HIV-1, interfere. We used CXCR4 and the LIF signaling receptor (gp130)-expressing cMAGI cells transfected with CD4, CCR5, and HIV-LTR-β-galactosidase as a model system to investigate the potential involvement of Stat proteins in the anti-HIV-1 effect of LIF. Pretreatment with recombinant human (rh)LIF resulted in a significantly reduced uptake of HIV-1BaL, HIV-1LAI, and SIVmac251 viral particles without affecting uptake of murine leukemia retroviral particles. HIV-1BaL, HIV-1LAI, as well as rhLIF selectively induced phosphorylation of Stat 3 but not Stat 1 or Stat 5. However, treatment of cMAGI cells with rhLIF prior to HIV-1 infection downregulated the HIV-1-mediated Stat 3 phosphorylation. In addition, peripheral blood mononuclear cells (PBMCs) transfected with Stat 3 siRNA prior to HIV-1LAIor HIV-1BaLinfection produced significantly less HIV-1 p24 antigen as compared to nontransfected HIV-1LAIand HIV-1BaL-infected PBMCs. Thus, the JakStat signaling pathway is important for the HIV-1 replication life cycle and rhLIF excerts its anti-HIV-1 activity by disrupting this signaling cascade. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08892229
- Volume :
- 23
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- AIDS Research & Human Retroviruses
- Publication Type :
- Academic Journal
- Accession number :
- 24695841
- Full Text :
- https://doi.org/10.1089/aid.2006.0100