Microtubule plus end-associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells.
Microtubule plus end-associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells.
复制标题
DOI：
10.1083/jcb.201505123
复制
发表时间：
2015-10-26
期刊：
影响因子：
--
通讯作者：
Walsh D
中科院分区：
文献类型：
--
作者：
Jovasevic V;Naghavi MH;Walsh D
Herpes simplex virus particles that enter the cell do not randomly associate with microtubule filaments, but require plus end–binding proteins EB1, CLIP-170, and dynactin to initiate retrograde transport to the nucleus. Dynamic microtubules (MTs) continuously explore the intracellular environment and, through specialized plus end–tracking proteins (+TIPs), engage a variety of targets. However, the nature of cargoes that require +TIP-mediated capture for their movement on MTs remains poorly understood. Using RNA interference and dominant-negative approaches, combined with live cell imaging, we show that herpes simplex virus particles that have entered primary human cells exploit a +TIP complex comprising end-binding protein 1 (EB1), cytoplasmic linker protein 170 (CLIP-170), and dynactin-1 (DCTN1) to initiate retrograde transport. Depletion of these +TIPs completely blocked post-entry long-range transport of virus particles and suppressed infection ∼5,000-fold, whereas transferrin uptake, early endosome organization, and dynein-dependent movement of lysosomes and mitochondria remained unaffected. These findings provide the first insights into the earliest stages of viral engagement of MTs through specific +TIPs, akin to receptors, with therapeutic implications, and identify herpesvirus particles as one of a very limited number of cargoes absolutely dependent on CLIP-170–mediated capture to initiate transport in primary human cells.
