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Role of hsv-1 capsid vertex-specific component (Cvsc) and viral terminal dna in capsid docking at the nuclear pore

Villanueva-Valencia, José Ramon LU ; Tsimtsirakis, Efthymios LU and Evilevitch, Alex LU orcid (2021) In Viruses 13(12).
Abstract

Penetration of the viral genome into a host cell nucleus is critical for initiation of viral replication for most DNA viruses and a few RNA viruses. For herpesviruses, viral DNA ejection into a nucleus occurs when the capsid docks at the nuclear pore complex (NPC) basket with the correct orientation of the unique capsid portal vertex. It has been shown that capsid vertex-specific component (CVSC) proteins, which are located at the twelve vertices of the human herpes simplex virus type 1 (HSV-1) capsid, interact with nucleoporins (Nups) of NPCs. However, it remained unclear whether CVSC proteins determine capsid-to-NPC binding. Furthermore, it has been speculated that terminal DNA adjacent to the portal complex of DNA-filled C-capsids... (More)

Penetration of the viral genome into a host cell nucleus is critical for initiation of viral replication for most DNA viruses and a few RNA viruses. For herpesviruses, viral DNA ejection into a nucleus occurs when the capsid docks at the nuclear pore complex (NPC) basket with the correct orientation of the unique capsid portal vertex. It has been shown that capsid vertex-specific component (CVSC) proteins, which are located at the twelve vertices of the human herpes simplex virus type 1 (HSV-1) capsid, interact with nucleoporins (Nups) of NPCs. However, it remained unclear whether CVSC proteins determine capsid-to-NPC binding. Furthermore, it has been speculated that terminal DNA adjacent to the portal complex of DNA-filled C-capsids forms a structural motif with the portal cap (which retains DNA in the capsid), which mediates capsid-NPC binding. We demonstrate that terminal viral DNA adjacent to the portal proteins does not present a structural element required for capsid-NPC binding. Our data also show that level of CVSC proteins on the HSV-1 capsid affects level of NPC binding. To elucidate the capsid-binding process, we use an isolated, reconstituted cell nucleus system that recapitulates capsid-nucleus binding in vivo without interference from trafficking kinetics of capsids moving toward the nucleus. This allows binding of non-infectious capsid maturation intermediates with varying levels of vertex-specific components. This experimental system provides a platform for investigating virus–host interaction at the nuclear membrane.

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Please use this url to cite or link to this publication:
author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Capsid vertex-specific component (CVSC), DNA ejection, HSV-1, Nuclear pore complex, UL25, UL36
in
Viruses
volume
13
issue
12
article number
2515
publisher
MDPI AG
external identifiers
  • pmid:34960783
  • scopus:85121441024
ISSN
1999-4915
DOI
10.3390/v13122515
language
English
LU publication?
yes
id
d38f6bc0-bb8d-4433-9c2b-d78ebd1d8ea3
date added to LUP
2022-01-26 14:52:08
date last changed
2024-06-16 00:32:40
@article{d38f6bc0-bb8d-4433-9c2b-d78ebd1d8ea3,
  abstract     = {{<p>Penetration of the viral genome into a host cell nucleus is critical for initiation of viral replication for most DNA viruses and a few RNA viruses. For herpesviruses, viral DNA ejection into a nucleus occurs when the capsid docks at the nuclear pore complex (NPC) basket with the correct orientation of the unique capsid portal vertex. It has been shown that capsid vertex-specific component (CVSC) proteins, which are located at the twelve vertices of the human herpes simplex virus type 1 (HSV-1) capsid, interact with nucleoporins (Nups) of NPCs. However, it remained unclear whether CVSC proteins determine capsid-to-NPC binding. Furthermore, it has been speculated that terminal DNA adjacent to the portal complex of DNA-filled C-capsids forms a structural motif with the portal cap (which retains DNA in the capsid), which mediates capsid-NPC binding. We demonstrate that terminal viral DNA adjacent to the portal proteins does not present a structural element required for capsid-NPC binding. Our data also show that level of CVSC proteins on the HSV-1 capsid affects level of NPC binding. To elucidate the capsid-binding process, we use an isolated, reconstituted cell nucleus system that recapitulates capsid-nucleus binding in vivo without interference from trafficking kinetics of capsids moving toward the nucleus. This allows binding of non-infectious capsid maturation intermediates with varying levels of vertex-specific components. This experimental system provides a platform for investigating virus–host interaction at the nuclear membrane.</p>}},
  author       = {{Villanueva-Valencia, José Ramon and Tsimtsirakis, Efthymios and Evilevitch, Alex}},
  issn         = {{1999-4915}},
  keywords     = {{Capsid vertex-specific component (CVSC); DNA ejection; HSV-1; Nuclear pore complex; UL25; UL36}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{MDPI AG}},
  series       = {{Viruses}},
  title        = {{Role of hsv-1 capsid vertex-specific component (Cvsc) and viral terminal dna in capsid docking at the nuclear pore}},
  url          = {{http://dx.doi.org/10.3390/v13122515}},
  doi          = {{10.3390/v13122515}},
  volume       = {{13}},
  year         = {{2021}},
}