| Item type |
文献 / Documents(1) |
| 公開日 |
2021-12-14 |
| アクセス権 |
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|
アクセス権 |
open access |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
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|
関連識別子 |
https://doi.org/10.1128/JVI.02177-20 |
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|
関連名称 |
10.1128/JVI.02177-20 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Species-Specific Valid Ternary Interactions of HIV-1 Env-gp120, CD4, and CCR5 as Revealed by an Adaptive Single-Amino Acid Substitution at the V3 Loop Tip |
| タイトル別表記 |
|
|
その他のタイトル |
V3 Tip-Dependent Species Specificity of HIV-1 Env |
| 著者 |
駒, 貴明
ヨコヤマ, マサル
コタニ, オサム
土肥, 直哉
ナカニシ, ニナ
オオクボ, ハヤト
足立, 隼
足立, 昭夫
サトウ, ヒロノリ
野間口, 雅子
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| 抄録 |
|
|
内容記述 |
Molecular interactions of the variable envelope gp120 subunit of HIV-1 with two cellular receptors are the first step of viral infection, thereby playing pivotal roles in determining viral infectivity and cell tropism. However, the underlying regulatory mechanisms for interactions under gp120 spontaneous variations largely remain unknown. Here, we show an allosteric mechanism in which a single gp120 mutation remotely controls the ternary interactions between gp120 and its receptors for the switch of viral cell tropism. Virological analyses showed that a G310R substitution at the tip of the gp120 V3 loop selectively abolished the viral replication ability in human cells, despite evoking enhancement of viral replication in macaque cells. Molecular dynamics (MD) simulations predicted that the G310R substitution at a site away from the CD4 interaction site selectively impeded the binding ability of gp120 to human CD4. Consistently, virions with the G310R substitution exhibited a reduced binding ability to human lymphocyte cells. Furthermore, the G310R substitution influenced the gp120-CCR5 interaction in a CCR5-type dependent manner as assessed by MD simulations and an infectivity assay using exogenously expressed CCR5s. Interestingly, an I198M mutation in human CCR5 restored the infectivity of the G310R virus in human cells. Finally, MD simulation predicted amino acid interplays that physically connect the V3 loop and gp120 elements for the CD4 and CCR5 interactions. Collectively, these results suggest that the V3 loop tip is a cis-allosteric regulator that remotely controls intra- and intermolecular interactions of HIV-1 gp120 for balancing ternary interactions with CD4 and CCR5. |
| キーワード |
|
|
主題 |
HIV-1 |
| キーワード |
|
|
主題 |
Env-gp120 |
| キーワード |
|
|
主題 |
CD4 |
| キーワード |
|
|
主題 |
CCR5 |
| キーワード |
|
|
主題 |
V3 loop |
| キーワード |
|
|
主題 |
adaptive mutation |
| キーワード |
|
|
主題 |
species specificity |
| キーワード |
|
|
主題 |
in silico structural analysis |
| 書誌情報 |
en : Journal of Virology
巻 95,
号 13,
p. e02177-20,
発行日 2021-06-10
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
10985514 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12024806 |
| 出版者 |
|
|
出版者 |
American Society for Microbiology |
| EID |
|
|
識別子 |
375129 |
| 言語 |
|
|
言語 |
eng |
JVI_95_13_e02177-20.pdf (3.46 MB)
