title: The herpesvirus VP1/2 protein is an effector of dynein-mediated capsid transport and neuroinvasion.
abstract: Microtubule transport of herpesvirus capsids from the cell periphery to the nucleus is imperative for viral replication and, in the case of many alphaherpesviruses, transmission into the nervous system. Using the neuroinvasive herpesvirus, pseudorabies virus (PRV), we show that the viral protein 1/2 (VP1/2) tegument protein associates with the dynein/dynactin microtubule motor complex and promotes retrograde microtubule transport of PRV capsids. Functional activation of VP1/2 requires binding to the capsid protein pUL25 or removal of the capsid-binding domain. A proline-rich sequence within VP1/2 is required for the efficient interaction with the dynein/dynactin microtubule motor complex as well as for PRV virulence and retrograde axon transport in vivo. Additionally, in the absence of infection, functionally active VP1/2 is sufficient to move large surrogate cargoes via the dynein/dynactin microtubule motor complex. Thus, VP1/2 tethers PRV capsids to dynein/dynactin to enhance microtubule transport, neuroinvasion, and pathogenesis.
authors: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Sofia V
authors: SV
authors: Zaichick
authors: Kevin P
authors: KP
authors: Bohannon
authors: Ami
authors: A
authors: Hughes
authors: Patricia J
authors: PJ
authors: Sollars
authors: Gary E
authors: GE
authors: Pickard
authors: Gregory A
authors: GA
authors: Smith
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002522:Chlorocebus aethiops; D060085:Coinfection / Q000378:metabolism / Q000821:virology; D004398:Dyneins / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D011558:Herpesvirus 1, Suid / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism / Q000821:virology; D011392:Proline / Q000378:metabolism; D025941:Protein Interaction Mapping; D021381:Protein Transport; D011557:Pseudorabies / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051381:Rats; D020318:Rats, Long-Evans; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000821:virology*; D014709:Vero Cells; D010948:Viral Plaque Assay; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015678:Viral Structural Proteins; D049452:Green Fluorescent Proteins; D011392:Proline; D004398:Dyneins