Role of hsv-1 capsid vertex-specific component (Cvsc) and viral terminal dna in capsid docking at the nuclear pore
(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.
(Less)
- author
- Villanueva-Valencia, José Ramon
LU
; Tsimtsirakis, Efthymios LU and Evilevitch, Alex LU
- organization
- publishing date
- 2021
- 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
-
- scopus:85121441024
- pmid:34960783
- 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
- 2025-01-26 23:26:05
@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}}, }