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J Cell Biol. 2015 Oct 26;211(2):323-37. doi: 10.1083/jcb.201505123.

Microtubule plus end-associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells.

Author information

1
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
2
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032 derek.walsh@northwestern.edu mojgan.naghavi@northwestern.edu.
3
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 Department of Microbiology, School of Medicine, New York University, New York, NY 10016 derek.walsh@northwestern.edu mojgan.naghavi@northwestern.edu.

Abstract

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.

PMID:
26504169
PMCID:
PMC4621836
DOI:
10.1083/jcb.201505123
[Indexed for MEDLINE]
Free PMC Article

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