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

作     者：Ting Tu Jianbo Zhan Danlei Mou Wei Li Bin Su Tong Zhang Tao Li Ning Li Hao Wu Cong Jin Huabiao Chen 

作者机构：Jiangsu Key Laboratory of Clinical Laboratory MedicineJiangsu University School of MedicineZhenjiang 212013China National HIV/HCV Reference LaboratoryNational Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China Hubei Provincial Center for Disease Control and PreventionWuhan 430079China Beijing You'an HospitalCapital Medical UniversityBeijing 100069China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2017年第32卷第6期

页      面：485-494页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：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) China’s 12th Five-Year Major Project on the Prevention and Treatment of AIDS 

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

摘      要：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 ***, 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.