Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus

The molecular mechanism affecting translocation of newly synthesized herpesvirus nucleocapsids from the nucleus into the cytoplasm is still not fully understood. The viral nuclear egress complex (NEC) mediates budding at and scission from the inner nuclear membrane, but the NEC is not sufficient for...

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Main Authors: Anna D. Dorsch, Julia E. Hölper, Kati Franzke, Luca M. Zaeck, Thomas C. Mettenleiter, Barbara G. Klupp
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/6/1117
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author Anna D. Dorsch
Julia E. Hölper
Kati Franzke
Luca M. Zaeck
Thomas C. Mettenleiter
Barbara G. Klupp
author_facet Anna D. Dorsch
Julia E. Hölper
Kati Franzke
Luca M. Zaeck
Thomas C. Mettenleiter
Barbara G. Klupp
author_sort Anna D. Dorsch
collection DOAJ
description The molecular mechanism affecting translocation of newly synthesized herpesvirus nucleocapsids from the nucleus into the cytoplasm is still not fully understood. The viral nuclear egress complex (NEC) mediates budding at and scission from the inner nuclear membrane, but the NEC is not sufficient for efficient fusion of the primary virion envelope with the outer nuclear membrane. Since no other viral protein was found to be essential for this process, it was suggested that a cellular machinery is recruited by viral proteins. However, knowledge on fusion mechanisms involving the nuclear membranes is rare. Recently, vesicle-associated membrane protein-associated protein B (VAPB) was shown to play a role in nuclear egress of herpes simplex virus 1 (HSV-1). To test this for the related alphaherpesvirus pseudorabies virus (PrV), we mutated genes encoding VAPB and VAPA by CRISPR/Cas9-based genome editing in our standard rabbit kidney cells (RK13), either individually or in combination. Single as well as double knockout cells were tested for virus propagation and for defects in nuclear egress. However, no deficiency in virus replication nor any effect on nuclear egress was obvious suggesting that VAPB and VAPA do not play a significant role in this process during PrV infection in RK13 cells.
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spelling doaj.art-1a502f7b4495458fbe723b41c5da45852023-11-21T23:34:26ZengMDPI AGViruses1999-49152021-06-01136111710.3390/v13061117Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies VirusAnna D. Dorsch0Julia E. Hölper1Kati Franzke2Luca M. Zaeck3Thomas C. Mettenleiter4Barbara G. Klupp5Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, GermanyInstitute of Infectology, Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, GermanyInstitute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, GermanyThe molecular mechanism affecting translocation of newly synthesized herpesvirus nucleocapsids from the nucleus into the cytoplasm is still not fully understood. The viral nuclear egress complex (NEC) mediates budding at and scission from the inner nuclear membrane, but the NEC is not sufficient for efficient fusion of the primary virion envelope with the outer nuclear membrane. Since no other viral protein was found to be essential for this process, it was suggested that a cellular machinery is recruited by viral proteins. However, knowledge on fusion mechanisms involving the nuclear membranes is rare. Recently, vesicle-associated membrane protein-associated protein B (VAPB) was shown to play a role in nuclear egress of herpes simplex virus 1 (HSV-1). To test this for the related alphaherpesvirus pseudorabies virus (PrV), we mutated genes encoding VAPB and VAPA by CRISPR/Cas9-based genome editing in our standard rabbit kidney cells (RK13), either individually or in combination. Single as well as double knockout cells were tested for virus propagation and for defects in nuclear egress. However, no deficiency in virus replication nor any effect on nuclear egress was obvious suggesting that VAPB and VAPA do not play a significant role in this process during PrV infection in RK13 cells.https://www.mdpi.com/1999-4915/13/6/1117herpesviruspseudorabies virusPrVnuclear egressvesicle-associated membrane protein associated proteinVAPA
spellingShingle Anna D. Dorsch
Julia E. Hölper
Kati Franzke
Luca M. Zaeck
Thomas C. Mettenleiter
Barbara G. Klupp
Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus
Viruses
herpesvirus
pseudorabies virus
PrV
nuclear egress
vesicle-associated membrane protein associated protein
VAPA
title Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus
title_full Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus
title_fullStr Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus
title_full_unstemmed Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus
title_short Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus
title_sort role of vesicle associated membrane protein associated proteins vap a and vapb in nuclear egress of the alphaherpesvirus pseudorabies virus
topic herpesvirus
pseudorabies virus
PrV
nuclear egress
vesicle-associated membrane protein associated protein
VAPA
url https://www.mdpi.com/1999-4915/13/6/1117
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