Simonetti Francesco R, Sobolewski Michele D, Fyne Elizabeth, Shao Wei, Spindler Jonathan, Hattori Junko, Anderson Elizabeth M, Watters Sarah A, Hill Shawn, Wu Xiaolin, Wells David, Su Li, Luke Brian T, Halvas Elias K, Besson Guillaume, Penrose Kerri J, Yang Zhiming, Kwan Richard W, Van Waes Carter, Uldrick Thomas, Citrin Deborah E, Kovacs Joseph, Polis Michael A, Rehm Catherine A, Gorelick Robert, Piatak Michael, Keele Brandon F, Kearney Mary F, Coffin John M, Hughes Stephen H, Mellors John W, Maldarelli Frank
HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702; Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, 20157 Milan, Italy;
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261;
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1883-8. doi: 10.1073/pnas.1522675113. Epub 2016 Feb 8.
Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4(+) T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1-infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4(+)T cells can be a reservoir of infectious HIV-1.
尽管接受了多年的联合抗逆转录病毒疗法,传染性HIV-1的储存库仍然存在,这使得治愈HIV-1感染成为一项重大挑战。大多数前病毒DNA存在于CD4(+)T细胞中。其中一些CD4(+)T细胞发生了克隆性扩增;大多数前病毒存在缺陷。目前尚不清楚是否有任何克隆性扩增的细胞携带具有复制能力的前病毒。我们报告称,一个高度扩增的CD4(+)T细胞克隆含有一个完整的前病毒。这个高度扩增的克隆产生了传染性病毒,在一名患有鳞状细胞癌的HIV-1感染患者接受cART治疗期间,该病毒被检测为持续性血浆病毒血症。含有完整前病毒的细胞广泛分布,并且在癌症转移灶中显著富集。这些结果表明,克隆性扩增的CD4(+)T细胞可能是传染性HIV-1的一个储存库。