title: Herpes simplex virus 1 Us3 deletion mutant is infective despite impaired capsid translocation to the cytoplasm.
abstract: Herpes simplex virus 1 (HSV-1) capsids are assembled in the nucleus bud at the inner nuclear membrane into the perinuclear space, acquiring envelope and tegument. In theory, these virions are de-enveloped by fusion of the envelope with the outer nuclear membrane and re-enveloped by Golgi membranes to become infective. Us3 enables the nucleus to cytoplasm capsid translocation. Nevertheless, Us3 is not essential for the production of infective progeny viruses. Determination of phenotype distribution by quantitative electron microscopy, and calculation per mean nuclear or cell volume revealed the following: (i) The number of R7041(∆US3) capsids budding at the inner nuclear membrane was significantly higher than that of wild type HSV-1; (ii) The mean number of R7041(∆US3) virions per mean cell volume was 2726, that of HSV-1 virions 1460 by 24 h post inoculation; (iii) 98% of R7041(∆US3) virions were in the perinuclear space; (iv) The number of R7041(∆US3) capsids in the cytoplasm, including those budding at Golgi membranes, was significantly reduced. Cell associated R7041(∆US3) yields were 2.37×10(8) and HSV-1 yields 1.57×10(8) PFU/mL by 24 h post inoculation. We thus conclude that R7041(∆US3) virions, which acquire envelope and tegument by budding at the inner nuclear membrane into the perinuclear space, are infective.
authors.affiliation: Institute of Veterinar Anatomy, Winterthurerstrasse 260, CH-8057 Zürich, Switzerland. pewild@access.uzh.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Wild
authors.affiliation: Institute of Veterinar Anatomy, Winterthurerstrasse 260, CH-8057 Zürich, Switzerland. sabineleisinger@yahoo.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Leisinger
authors.affiliation: Institute of Virology, Winterthurerstrasse 266a, CH-8057 Zürich, Switzerland. annapaula.oliveira@gmail.com.
authors.forename: Anna Paula
authors.initials: AP
authors.lastname: de Oliveira
authors.affiliation: Institute of Veterinar Anatomy, Winterthurerstrasse 260, CH-8057 Zürich, Switzerland. emschra@vetanat.uzh.ch.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Schraner
authors.affiliation: Center for Microscopy and Image Analysis, Winterthurerstrasse 190,CH-8057 Zürich, Switzerland. andres.kaech@zmb.uzh.ch.
authors.forename: Andres
authors.initials: A
authors.lastname: Kaech
authors.affiliation: Institute of Virology, Winterthurerstrasse 266a, CH-8057 Zürich, Switzerland. Mathias.Ackermann@vetvir.uzh.ch.
authors.forename: Mathias
authors.initials: M
authors.lastname: Ackermann
authors.affiliation: Institute of Virology, Winterthurerstrasse 266a, CH-8057 Zürich, Switzerland. Kurt.Tobler@vetvir.uzh.ch.
authors.forename: Kurt
authors.initials: K
authors.lastname: Tobler
mesh_terms: D000818:Animals; D002213:Capsid / Q000648:ultrastructure; D002467:Cell Nucleus; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000821:virology; D017353:Gene Deletion; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D008854:Microscopy, Electron; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency*; D014709:Vero Cells; D019562:Viral Load; D014764:Viral Proteins; D014771:Virion / Q000648:ultrastructure; D019065:Virus Assembly; D057074:Virus Release
chemical_list: D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C095207:US3 protein, Human herpesvirus 1