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

Vladimir Jovasevic, Mojgan H. Naghavi, Derek Walsh*

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)323-337
Number of pages15
JournalJournal of Cell Biology
Volume211
Issue number2
DOIs
StatePublished - Oct 26 2015

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Microtubule plus end-associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells'. Together they form a unique fingerprint.

  • Cite this