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. 2017 Sep 15;32(6):485–494. doi: 10.1007/s12250-017-3992-9

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

Ting Tu 1,2,#, Jianbo Zhan 3,#, Danlei Mou 4, Wei Li 4, Bin Su 4, Tong Zhang 4, Tao Li 1, Ning Li 4, Hao Wu 4, Cong Jin 2,✉, Huabiao Chen 1,✉
PMCID: PMC6599175  PMID: 28918477

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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Keywords: HIV-1 infection, viral replication, cytotoxic T lymphocyte (CTL), natural killer cells, neutralizing antibody

Acknowledgments

This work was supported by the Fund for Jiangsu Specially-Appointed Professor (2014JSTPJS-53), the Innovation Fund from National Center for AIDS/STD Control and Prevention, China CDC, Capital Medical University Key Laboratory Project (2-03-02-BJYAH 2016006), and China’s 12th Five-Year Major Project on the Prevention and Treatment of AIDS. Dr. Dennis Burton (the Scripps Research Institute) kindly provided b12, b12 LALA, and Den3 monoclonal antibodies. The HIV-1 strains X4 92HT599 and R5 91US056 were obtained from the AIDS Research and Reagent Program, Division of AIDS, NIAID, NIH.

Footnotes

These authors contributed equally to this work.

Contributor Information

Cong Jin, Email: jincongbj@163.com.

Huabiao Chen, Email: chenhuabiao@hotmail.com.

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