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Metadata ID
0100491738
Access Rights
open access
Version
Version of Record
Title
SARS-CoV-2 papain-like protease inhibits ISGylation of the viral nucleocapsid protein to evade host anti-viral immunity
Author
Rhamadianti, Aulia Fitri ; Abe, Takayuki ; Tanaka, Tomohisa ; Ono, Chikako ; Katayama, Hisashi ; Makino, Yoshiteru ; Deng, Lin ; Matsui, Chieko ; Moriishi, Kohji ; Shima, Fumi ; Matsuura, Yoshiharu ; Shoji, Ikuo
Author Name
Rhamadianti, Aulia Fitri
Author ID
A1961
NRID
1000090403203
Author Name
Abe, Takayuki
阿部, 隆之
アベ, タカユキ
Affiliation
医学研究科
Author Name
Tanaka, Tomohisa
Author Name
Ono, Chikako
Author Name
Katayama, Hisashi
Author ID
A2412
NRID
1000080822337
Author Name
Makino, Yoshiteru
槇野, 義輝
マキノ, ヨシテル
Affiliation
科学技術イノベーション研究科
Author ID
A0830
NRID
1000040437497
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail.html?systemId=e256bdfcb1f5fc23520e17560c007669
Author Name
Deng, Lin
鄧, 琳
トウ, リン
Affiliation
医学研究科
Author ID
A2224
NRID
1000070778414
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail.html?systemId=a7a5713302f41316520e17560c007669
Author Name
Matsui, Chieko
松井, 千絵子
マツイ, チエコ
Affiliation
医学研究科
Author Name
Moriishi, Kohji
Author ID
A0774
NRID
1000060335445
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail.html?systemId=ad9ff9c53a5d3608520e17560c007669
Author Name
Shima, Fumi
島, 扶美
シマ, フミ
Affiliation
科学技術イノベーション研究科
Author Name
Matsuura, Yoshiharu
Author ID
A0795
NRID
1000040356241
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail.html?systemId=72a067e0cb19ce45520e17560c007669
Author Name
Shoji, Ikuo
勝二, 郁夫
ショウジ, イクオ
Affiliation
医学研究科
language
English (英語)
Source Title
Journal of Virology
Volume (Issue)
98(9)
Page
e00855-24
Publisher
American Society for Microbiology
Date of Publication
2024-09-17
Date of Deposit
2025-02-09
Note
Published onlline: 2024-08-09
Abstract
A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes mild-to-severe respiratory symptoms, including acute respiratory distress. Despite remarkable efforts to investigate the virological and pathological impacts of SARS-CoV-2, many of the characteristics of SARS-CoV-2 infection still remain unknown. The interferon-inducible ubiquitin-like protein ISG15 is covalently conjugated to several viral proteins to suppress their functions. It was reported that SARS-CoV-2 utilizes its papain-like protease (PLpro) to impede ISG15 conjugation, ISGylation. However, the role of ISGylation in SARS-CoV-2 infection remains unclear. We aimed to elucidate the role of ISGylation in SARS-CoV-2 replication. We observed that the SARS-CoV-2 nucleocapsid protein is a target protein for the HERC5 E3 ligase-mediated ISGylation in cultured cells. Site-directed mutagenesis reveals that the residue K374 within the C-terminal spacer B-N3 (SB/N3) domain is required for nucleocapsid-ISGylation, alongside conserved lysine residue in MERS-CoV (K372) and SARS-CoV (K375). We also observed that the nucleocapsid-ISGylation results in the disruption of nucleocapsid oligomerization, thereby inhibiting viral replication. Knockdown of ISG15 mRNA enhanced SARS-CoV-2 replication in the SARS-CoV-2 reporter replicon cells, while exogenous expression of ISGylation components partially hampered SARS-CoV-2 replication. Taken together, these results suggest that SARS-CoV-2 PLpro inhibits ISGylation of the nucleocapsid protein to promote viral replication by evading ISGylation-mediated disruption of the nucleocapsid oligomerization.
Keywords
SARS-CoV-2
papain-like protease
nucleocapsid
ISG15
anti-viral activity
Category
Graduate School of Medicine
Graduate School of Science, Technology and Innovation
Journal Article
Rights
© 2024 American Society for Microbiology. All Rights Reserved.
Relation
DOI
https://doi.org/10.1128/jvi.00855-24
PMID
39120134
Local
0100490883