title: Dystonin/BPAG1 promotes plus-end-directed transport of herpes simplex virus 1 capsids on microtubules during entry.
abstract: During infection by herpes simplex virus 1 (HSV-1), the viral capsid is transported around the cytoplasm along the microtubule (MT) network. Although molecular motors have been implicated in this process, the composition of the molecular machinery required for efficient directional transport is unknown. We previously showed that dystonin (BPAG1) is recruited to HSV-1 capsids by the capsid-bound tegument protein pUL37 to promote efficient cytoplasmic transport of capsids during egress. Dystonin is a cytoskeleton cross-linker which localizes at MT plus ends and has roles in retrograde and anterograde transport in neurons. In this study, we investigated the role of dystonin during the entry stages of HSV-1 infection. Because of the way in which the MT network is organized, capsids are required to change their direction of motion along the MTs as they travel from the point of entry to the nucleus, where replication takes place. Thus, capsids first travel to the centrosome (the principal microtubule organizing center) by minus-end-directed transport and then switch polarity and travel to the nucleus by plus-end-directed transport. We observed that transport of capsids toward the centrosome was slowed, but not blocked, by dystonin depletion. However, transport of capsids away from the centrosome was significantly impaired, causing them to accumulate in the vicinity of the centrosome and reducing the numbers reaching the nucleus. We conclude that, during entry of HSV-1, dystonin has a specific role in plus-ended transport of capsids from the centrosome to the nucleus.
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
authors.forename: Marion
authors.initials: M
authors.lastname: McElwee
authors.forename: Frauke
authors.initials: F
authors.lastname: Beilstein
authors.forename: Marc
authors.initials: M
authors.lastname: Labetoulle
authors.forename: Frazer J
authors.initials: FJ
authors.lastname: Rixon
authors.forename: David
authors.initials: D
authors.lastname: Pasdeloup
mesh_terms: D000818:Animals; D002213:Capsid / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D000071821:Dystonin; D018259:Herpesvirus 1, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C486268:DST protein, human; D000071821:Dystonin; D009419:Nerve Tissue Proteins
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