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Activity of superior interferon α against HIV-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes

ZHANG Wei TONG Xiao Tadashi Nakasone YUE Xue-tian Naoki Yamamoto LIU Xin-yuan YANG Rong-ge

中华医学杂志(英文版)2011,Vol.124Issue(3):396-400,5.
中华医学杂志(英文版)2011,Vol.124Issue(3):396-400,5.DOI:10.3760/cma.j.issn.0366-6999.2011.03.014

Activity of superior interferon α against HIV-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes

Activity of superior interferon α against HIV-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes

ZHANG Wei 1TONG Xiao 1Tadashi Nakasone 2YUE Xue-tian 3Naoki Yamamoto 2LIU Xin-yuan 3YANG Rong-ge4

作者信息

  • 1. Laboratory of HIV Molecular Epidemiology and Virology, State Key Laboratory of Virology, Wuhan Institution of Virology,Chinese Academy of Sciences, Wuhan, Hubei 430071, China
  • 2. AIDS Research Center, National Institute of Infectious Diseases,1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
  • 3. Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, China
  • 4. Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences, Shanghai 200031, China
  • 折叠

摘要

Abstract

Background Interferon (IFN) can inhibit human immunodeficiency virus type 1 (HIV-1) replication in vitro and in clinic.However, IFN therapy for HIV infection was limited by its moderate antiviral efficacy and its frequent adverse effects. In the present study we evaluated the anti-HIV efficacy of a novel synthesized superior interferon α (slFNα).Methods We performed in vitro experiments with HIV-1 IIB infected MT4 cells, and evaluated in vivo anti-HIV efficacy of slFNα in severe combined immunodeficient (SClD) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SClD mice).Results We found that the 50% effective concentrations (EC5o) of slFNα against the replication of HIV-1 in MT4 cells was 0.06 ng/ml, representing stronger antiviral activity than interferon-α in vitro. In the hu-PBL-SCID mice, a dose-dependent protection pattern was observed: with 0.45 μg and 1.35 μg slFNα daily treatments, parts of SCID mice were protected from HIV infection, whereas 2.25 μg sIFNα daily treatments resulted in a terminally complete protection.Conclusions slFNα shows good anti-HIV activity both in vitro and in SCID mice, may be a promising anti-HIV agent deserving clinical investigation, especially considering the potential of IFN-α to inhibit HIV replication in patients infected with drug-resistant variants or co-infected with hepatitis C virus (HCV).

关键词

human immunodeficiency virus type 1/severe combined immunodeficient mouse/interferon-α

Key words

human immunodeficiency virus type 1/severe combined immunodeficient mouse/interferon-α

引用本文复制引用

ZHANG Wei,TONG Xiao,Tadashi Nakasone,YUE Xue-tian,Naoki Yamamoto,LIU Xin-yuan,YANG Rong-ge..Activity of superior interferon α against HIV-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes[J].中华医学杂志(英文版),2011,124(3):396-400,5.

基金项目

This work was supported by the grants from the National Grand Program on Key Infectious Disease (No. 2008ZX10001-002), the China National Program on Key Basic Research Projects (973 Program) (No. 2005CB22903 and No. 2006CB504202), and the China Ministry of Science and Technology. (No. 2008ZX10001-002)

中华医学杂志(英文版)

OACSCDCSTPCDMEDLINESCI

0366-6999

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