title: Pseudorabies virus US3 leads to filamentous actin disassembly and contributes to viral genome delivery to the nucleus.
abstract: The conserved alphaherpesvirus US3 tegument protein induces rearrangements of the actin cytoskeleton, consisting of protrusion formation and stress fiber breakdown. Although US3 does not affect levels of total actin protein, it remains unclear whether US3 modulates the total levels of filamentous (F) actin. In this report, we show that the pseudorabies virus (PRV) US3 protein, via its kinase activity, leads to disassembly of F-actin in porcine ST cells. F-actin disassembly has been reported before to contribute to host cell entry of HIV. In line with this, in the current study, we report that US3 has a previously uncharacterized role in viral genome delivery to the nucleus, since quantitative polymerase chain reaction (qPCR) assays on nuclear fractions demonstrated a reduced nuclear delivery of US3null PRV compared to wild type PRV genomes. Treatment of cells with the actin depolymerizing drug cytochalasin D enhanced virus genome delivery to the nucleus, particularly of US3null PRV, supporting a role for F-actin disassembly during certain aspects of viral entry. In conclusion, the US3 kinase of PRV leads to F-actin depolymerization, and US3 and F-actin disassembly contribute to viral genome delivery to the nucleus.
authors: Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors: Thary
authors: T
authors: Jacob
authors: Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors: Céline
authors: C
authors: Van den Broeke
authors: Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors: Korneel
authors: K
authors: Grauwet
authors: Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors: Kim
authors: K
authors: Baert
authors: Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors: Christophe
authors: C
authors: Claessen
authors: Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors: Steffi
authors: S
authors: De Pelsmaeker
authors: Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors: Cliff
authors: C
authors: Van Waesberghe
authors: Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. Electronic address: herman.favoreel@ugent.be.
authors: Herman W
authors: HW
authors: Favoreel
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D016679:Genome, Viral / Q000187:drug effects; D011558:Herpesvirus 1, Suid / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011557:Pseudorabies / Q000821:virology; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D013552:Swine; D013737:Testis / Q000166:cytology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics; D053586:Virus Internalization
chemical_list: D000199:Actins; D014764:Viral Proteins; D015638:Cytochalasin D; D017346:Protein Serine-Threonine Kinases
keywords: Actin; Entry; Pseudorabies virus; US3