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英国科学家的一项最新研究发现,人体T细胞之间的丝状联接或许为HIV攻陷人类免疫系统搭了桥。这种被命名为“膜纳米管”(membrane nanotubes)的新确定结构有助于解释HIV病毒如何快速有效地感染人类免疫细胞。相关论文1月13日在线发表于《自然—细胞生物学》(Nature Cell Biology)上。
进行该项研究的是英国伦敦帝国理工学院(Imperial College London)和牛津大学的科学家,他们通过实验室研究发现,当人类T细胞相互碰撞又分开时,有一定几率会在细胞膜之间形成一条很长的丝,这也成为了两个细胞间的一条通路。研究表明,这些丝甚至能够延伸到几个细胞长度,而且3D模拟研究发现,这些丝十分柔韧,能够弯曲,从而维持细胞的联接。
随后,研究人员利用荧光蛋白标记的HIV感染其中的一些T细胞,结果观测到HIV能够沿着该“纳米管”从已感染细胞移动向未感染细胞。
此前科学家已经在神经元和其他一些免疫细胞之间发现了这种联接,但最新的研究首次证实了T细胞间也能发生类似的联系。值得一提的是,由于联接点存在差异,新发现的“纳米管”与细胞分裂时出现的丝状结构并不相同,新确定的结构是由细胞膜材料交汇在一起。
研究人员表示,如果能够证实相同的机制发生在人体内,那么该结果将有助于解释为何细胞外的抗体无法有效抵御HIV病毒。
论文高级作者、伦敦帝国理工学院的Dan Davis教授表示,“新的发现表明,人体内还有科学家尚未发现的细胞通信方式。不过,我们在实验室中的初步研究结果并不能完全反映人体内的确切情况。如果事实果真如此,那无疑将为抗艾滋病药物的开发开辟一条林荫大道。”(科学网 任霄鹏/编译)
原始出处:
Nature Cell Biology
Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission
Stefanie Sowinski1, Clare Jolly2, Otto Berninghausen1, Marco A. Purbhoo1, Anne Chauveau1, Karsten Köhler1, Stephane Oddos1, Philipp Eissmann1, Frances M. Brodsky3, Colin Hopkins1, Björn Önfelt4, Quentin Sattentau2 & Daniel M. Davis1
1 Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ, UK.
2 Sir William Dunn School of Pathology, University of Oxford, OX1 3RE, UK.
3 The G. W. Hooper Foundation, Box 0552, 513 Parnassus Avenue, UCSF, San Francisco, CA 94143–0552, USA.
4 Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, S-171 77 Stockholm, Sweden.
Correspondence should be addressed to Daniel M. Davis d.davis@imperial.ac.uk
Transmission of HIV-1 via intercellular connections has been estimated as 100–1000 times more efficient than a cell-free process, perhaps in part explaining persistent viral spread in the presence of neutralizing antibodies1, 2. Such effective intercellular transfer of HIV-1 could occur through virological synapses3, 4, 5 or target-cell filopodia connected to infected cells6. Here we report that membrane nanotubes, formed when T cells make contact and subsequently part, provide a new route for HIV-1 transmission. Membrane nanotubes are known to connect various cell types, including neuronal and immune cells7, 8, 9, 10, 11, 12, 13, and allow calcium-mediated signals to spread between connected myeloid cells9. However, T-cell nanotubes are distinct from open-ended membranous tethers between other cell types7, 12, as a dynamic junction persists within T-cell nanotubes or at their contact with cell bodies. We also report that an extracellular matrix scaffold allows T-cell nanotubes to adopt variably shaped contours. HIV-1 transfers to uninfected T cells through nanotubes in a receptor-dependent manner. These data lead us to propose that HIV-1 can spread using nanotubular connections formed by short-term intercellular unions in which T cells specialize.
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