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

Vladimir Jovasevic1, Mojgan H Naghavi2, Derek Walsh3

  • 1Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.

Insights

Herpes simplex virus uses specific plus-end tracking proteins (EB1, CLIP-170, DCTN1) to initiate transport in human cells. Blocking these proteins severely inhibits viral infection and long-range movement.

Area of Science:

  • Cell Biology
  • Virology
  • Molecular Biology

Background:

  • Dynamic microtubules (MTs) are crucial for intracellular transport.
  • Plus-end tracking proteins (+TIPs) mediate interactions between MTs and cellular components.
  • The role of +TIPs in viral particle transport is not well understood.

Purpose of the Study:

  • To investigate the mechanism by which herpes simplex virus (HSV) initiates intracellular transport.
  • To identify the specific +TIPs involved in the early stages of HSV post-entry transport.
  • To determine the functional significance of +TIP-mediated capture for HSV infection.

Main Methods:

  • Utilized RNA interference and dominant-negative approaches to deplete specific +TIPs.
  • Employed live cell imaging to track the movement of HSV particles.
  • Assessed the impact of +TIP depletion on viral infection rates and other cellular transport processes.

Main Results:

  • Herpes simplex virus particles utilize a +TIP complex (EB1, CLIP-170, DCTN1) for retrograde transport initiation.
  • Depletion of these +TIPs completely blocked HSV long-range transport and reduced infection by ~5,000-fold.
  • Other cellular transport processes, including transferrin uptake and lysosome/mitochondria movement, were unaffected.

Conclusions:

  • HSV particles engage MTs via specific +TIPs, acting as essential receptors for initiating transport.
  • This +TIP-mediated capture is critical for HSV post-entry movement and infection establishment.
  • Herpesvirus particles represent a rare cargo class absolutely dependent on CLIP-170 for transport initiation, suggesting potential therapeutic targets.

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