Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals
Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals
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DOI：
10.1073/pnas.95.3.1201
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发表时间：
1998-02-03
影响因子：
11.1
通讯作者：
Nabel, GJ
中科院分区：
文献类型：
--
作者：
Ranga, U;Woffendin, C;Nabel, GJ
抑制病毒复制的基因产物的细胞内表达有可能补充当前治疗艾滋病的抗病毒方法。我们之前已经证明，必需病毒蛋白 Rev M10 的突变抑制形式可以延长 HIV 感染者中用非病毒载体转导的 T 细胞的存活时间。因为这些基因修饰的细胞在超过 8 周的患者中没有观察到，所以努力提高植入的持续时间。在这项研究中，我们使用 Rev M10 的逆转录病毒载体递送在一项针对三名 HIV 血清阳性患者的初步研究中，将 M10 转化为 CD4(+) 细胞并分析了相关的免疫反应，DNA 和 RNA PCR 分析表明，在所有三名患者中，用 Rev M10 逆转录病毒载体转导的细胞存活并表达重组基因的时间明显长于用阴性对照载体转导的细胞。 Rev M10 或莫洛尼鼠白血病病毒 gp70 包膜蛋白均未检测到免疫反应，逆转录病毒基因转移后平均 6 个月才检测到 Rev M10 转导的细胞，而之前报道的非病毒载体递送大约需要 3 周。这些发现表明，抗病毒基因的逆转录病毒递送可能有助于 AIDS 的免疫重建，并可以提供更有效的载体来延长 HIV 中 CD4(+) 细胞的存活感染。
Intracellular expression of gene products that inhibit viral replication have the potential to complement current antiviral approaches to the treatment of AIDS, We previously have shown that a mutant inhibitory form of an essential viral protein, Rev M10, prolongs the survival of T cells transduced with a nonviral vector in HIV-infected individuals, Because these gene-modified cells were not observed in patients beyond 8 weeks, efforts were made to improve the duration of engraftment, In this study, we used retroviral vector delivery of Rev M10 to CD4(+) cells and analyzed relevant immune responses in a pilot study of three HIV seropositive patients, DNA and RNA PCR analyses revealed that cells transduced with Rev M10 retroviral vectors survived and expressed the recombinant gene for significantly longer time periods than those transduced with a negative control vector in all three patients. Immune responses were not detected either to Rev M10 or to Moloney murine leukemia virus gp70 envelope protein, Rev M10-transduced cells were detected for an average of 6 months after retroviral gene transfer compared with approximate to 3 weeks for the previously reported nonviral vector delivery, These findings suggest that retroviral delivery of an antiviral gene may potentially contribute to immune reconstitution in AIDS and could provide a more effective vector to prolong survival of CD4(+) cells in HIV infection.