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Volume 32 Issue 6
December 2017
    Citation: Ting Tu, Jianbo Zhan, Danlei Mou, Wei Li, Bin Su, Tong Zhang, Tao Li, Ning Li, Hao Wu, Cong Jin, Huabiao Chen. In vitro inhibition of HIV-1 replication in autologous CD4+ T cells indicates viral containment by multifactorial mechanisms .VIROLOGICA SINICA, 2017, 32(6) : 485-494.  http://dx.doi.org/10.1007/s12250-017-3992-9
    shu

    In vitro inhibition of HIV-1 replication in autologous CD4+ T cells indicates viral containment by multifactorial mechanisms

    Inhibition of HIV-1 replication by multifactorial mechanisms

    cstr: 32224.14.s12250-017-3992-9
    • 1.

      Jiangsu Key Laboratory of Clinical Laboratory Medicine, Jiangsu University School of Medicine , Zhenjiang 212013, China

    • 2.

      National HIV/HCV Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China

    • 3.

      Hubei Provincial Center for Disease Control and Prevention,Wuhan 430079, China

    • 4.

      Beijing You’an Hospital, Capital Medical University, Beijing 100069, China

    • Corresponding author: Cong Jin, jincongbj@163.com, ORCID: 0000-0002-5200-5992
      Huabiao Chen, chenhuabiao@hotmail.com, ORCID: 0000-0002-7215-5429
    • These authors contributed equally to this work.
    • Received Date: 05 April 2017
      Accepted Date: 27 July 2017
      Published Date: 15 September 2017
      Available online: 01 December 2017
    • HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4+ T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures. However, the same neutralizing antibody was able to contain viruses by antibody-dependent cell-mediated virus inhibition in vitro, which was mediated by natural killer cells (NKs) and dependent on an Fc-Fc receptor interaction. Meanwhile, bulk CTLs from HIV-1 controllers were more effective in suppression of virus replication than those from progressors. These findings indicate that control of HIV-1 replication in activated CD4+ T cells is ineffectively mediated by neutralizing antibodies alone, but that both CTLs and antibody-dependent NK-mediated immune mechanisms contribute to viral containment. Our study systemically compared three major players in controlling HIV-1 infection, CTLs, NAbs, and NKs, in an autologous system and highlighted the multifactorial mechanisms for viral containment and vaccine success.
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      In vitro inhibition of HIV-1 replication in autologous CD4+ T cells indicates viral containment by multifactorial mechanisms

        Corresponding author: Cong Jin, jincongbj@163.com
        Corresponding author: Huabiao Chen, chenhuabiao@hotmail.com
      • 1. Jiangsu Key Laboratory of Clinical Laboratory Medicine, Jiangsu University School of Medicine , Zhenjiang 212013, China
      • 2. National HIV/HCV Reference Laboratory, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
      • 3. Hubei Provincial Center for Disease Control and Prevention,Wuhan 430079, China
      • 4. Beijing You’an Hospital, Capital Medical University, Beijing 100069, China
      • Received Date: 05 April 2017
      • Accepted Date: 27 July 2017
      • Published Date: 15 September 2017

      Abstract: HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4+ T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures. However, the same neutralizing antibody was able to contain viruses by antibody-dependent cell-mediated virus inhibition in vitro, which was mediated by natural killer cells (NKs) and dependent on an Fc-Fc receptor interaction. Meanwhile, bulk CTLs from HIV-1 controllers were more effective in suppression of virus replication than those from progressors. These findings indicate that control of HIV-1 replication in activated CD4+ T cells is ineffectively mediated by neutralizing antibodies alone, but that both CTLs and antibody-dependent NK-mediated immune mechanisms contribute to viral containment. Our study systemically compared three major players in controlling HIV-1 infection, CTLs, NAbs, and NKs, in an autologous system and highlighted the multifactorial mechanisms for viral containment and vaccine success.

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