title: Equine herpesvirus type 1 (EHV-1) utilizes microtubules, dynein, and ROCK1 to productively infect cells.
abstract: To initiate infection, equine herpesvirus type 1 (EHV-1) attaches to heparan sulfate on cell surfaces and then interacts with a putative glycoprotein D receptor(s). After attachment, virus entry occurs either by direct fusion of the virus envelope with the plasma membrane or via endocytosis followed by fusion between the virus envelope and an endosomal membrane. Upon fusion, de-enveloped virus particles are deposited into the cytoplasm and travel to the nucleus for viral replication. In this report, we examined the mechanism of EHV-1 intracellular trafficking and investigated the ability of EHV-1 to utilize specific cellular components to efficiently travel to the nucleus post-entry. Using a panel of microtubule-depolymerizing drugs and inhibitors of microtubule motor proteins, we show that EHV-1 infection is dependent on both the integrity of the microtubule network and the minus-end microtubule motor protein, dynein. In addition, we show that EHV-1 actively induces the acetylation of tubulin, a marker of microtubule stabilization, as early as 15 min post-infection. Finally, our data support a role for the cellular kinase, ROCK1, in virus trafficking to the nucleus.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261, United States. framptona@uncw.edu
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Frampton
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Uchida
authors.forename: Jens
authors.initials: J
authors.lastname: von Einem
authors.forename: William F
authors.initials: WF
authors.lastname: Goins
authors.forename: Paola
authors.initials: P
authors.lastname: Grandi
authors.forename: Justus B
authors.initials: JB
authors.lastname: Cohen
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Osterrieder
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Glorioso
mesh_terms: D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004398:Dyneins / Q000378:metabolism*; D004861:Herpesvirus 1, Equid / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006736:Horses; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism*; D011817:Rabbits; D014404:Tubulin / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D014404:Tubulin; D054460:rho-Associated Kinases; D004398:Dyneins