Nuclear envelope impairment is facilitated by the herpes simplex virus 1 Us3 kinase
| Autor: | Mathias Ackermann, Andres Kaech, Anna Paula de Oliveira, Cornel Fraevel, Elisabeth M. Schraner, Sabine Leisinger, Jana Doehner, Peter J. Wild |
|---|---|
| Přispěvatelé: | University of Zurich, Wild, Peter |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
1 egress nuclear envelope breakdown fusion 10077 Institute of Veterinary Anatomy Nuclear Envelope viruses 030106 microbiology budding Herpesvirus 1 Human Protein Serine-Threonine Kinases medicine.disease_cause General Biochemistry Genetics and Molecular Biology 3000 General Pharmacology Toxicology and Pharmaceutics 03 medical and health sciences Viral Proteins HSV-1 egress Capsid 1300 General Biochemistry Genetics and Molecular Biology 2400 General Immunology and Microbiology medicine Inner membrane Humans General Pharmacology Toxicology and Pharmaceutics Nuclear pore General Immunology and Microbiology Super-resolution microscopy Chemistry nuclear pores HSV Wild type Herpes Simplex General Medicine Articles intraluminal transport Cell biology Cytosol 030104 developmental biology Herpes simplex virus medicine.anatomical_structure Cytoplasm 570 Life sciences biology 10024 Center for Microscopy and Image Analysis Nucleus 10244 Institute of Virology Research Article |
| Zdroj: | F1000Research |
| ISSN: | 2046-1402 |
| Popis: | Background: Capsids of herpes simplex virus 1 (HSV-1) are assembled in the nucleus, translocated either to the perinuclear space by budding at the inner nuclear membrane acquiring tegument and envelope, or released to the cytosol in a “naked” state via impaired nuclear pores that finally results in impairment of the nuclear envelope. The Us3 gene encodes a protein acting as a kinase, which is responsible for phosphorylation of numerous viral and cellular substrates. The Us3 kinase plays a crucial role in nucleus to cytoplasm capsid translocation. We thus investigate the nuclear surface in order to evaluate the significance of Us3 in maintenance of the nuclear envelope during HSV-1 infection.Methods: To address alterations of the nuclear envelope and capsid nucleus to cytoplasm translocation related to the function of the Us3 kinase we investigated cells infected with wild type HSV-1 or the Us3 deletion mutant R7041(∆Us3) by transmission electron microscopy, focused ion-beam electron scanning microscopy, cryo-field emission scanning electron microscopy, confocal super resolution light microscopy, and polyacrylamide gel electrophoresis.Results: Confocal super resolution microscopy and cryo-field emission scanning electron microscopy revealed decrement in pore numbers in infected cells. Number and degree of pore impairment was significantly reduced after infection with R7041(∆Us3) compared to infection with wild type HSV-1. The nuclear surface was significantly enlarged in cells infected with any of the viruses. Morphometric analysis revealed that additional nuclear membranes were produced forming multiple folds and caveolae, in which virions accumulated as documented by three-dimensional reconstruction after ion-beam scanning electron microscopy. Finally, significantly more R7041(∆Us3) capsids were retained in the nucleus than wild-type capsids whereas the number of R7041(∆Us3) capsids in the cytosol was significantly lower.Conclusions: The data indicate that Us3 kinase is involved in facilitation of nuclear pore impairment and, concomitantly, in capsid release through impaired nuclear envelope. |
| Databáze: | OpenAIRE |
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