Host E3 ligase HUWE1 attenuates the proapoptotic activity of the MERS-CoV accessory protein ORF3 by promoting its ubiquitin-dependent degradation.
J Biol Chem
; 298(2): 101584, 2022 02.
Статья
в английский
| MEDLINE | ID: covidwho-1699145
ABSTRACT
With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups nonstructural proteins, structural proteins, and accessory proteins. While the number of each of these proteins varies greatly among different coronaviruses, accessory proteins are most closely related to the pathogenicity of the virus. We found for the first time that the ORF3 accessory protein of MERS-CoV, which closely resembles the ORF3a proteins of severe acute respiratory syndrome coronavirus and SARS-CoV-2, has the ability to induce apoptosis in cells in a dose-dependent manner. Through bioinformatics analysis and validation, we revealed that ORF3 is an unstable protein and has a shorter half-life in cells compared to that of severe acute respiratory syndrome coronavirus and SARS-CoV-2 ORF3a proteins. After screening, we identified a host E3 ligase, HUWE1, that specifically induces MERS-CoV ORF3 protein ubiquitination and degradation through the ubiquitin-proteasome system. This results in the diminished ability of ORF3 to induce apoptosis, which might partially explain the lower spread of MERS-CoV compared to other coronaviruses. In summary, this study reveals a pathological function of MERS-CoV ORF3 protein and identifies a potential host antiviral protein, HUWE1, with an ability to antagonize MERS-CoV pathogenesis by inducing ORF3 degradation, thus enriching our knowledge of the pathogenesis of MERS-CoV and suggesting new targets and strategies for clinical development of drugs for MERS-CoV treatment.
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Полный текст:
Имеется в наличии
Коллекция:
Международные базы данных
база данных:
MEDLINE
Основная тема:
Viral Nonstructural Proteins
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Apoptosis
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Coronavirus Infections
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Tumor Suppressor Proteins
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Ubiquitin-Protein Ligases
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Ubiquitination
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Middle East Respiratory Syndrome Coronavirus
Тип исследования:
Экспериментальные исследования
/
Прогностическое исследование
/
Рандомизированные контролируемые испытания
Пределы темы:
Люди
Язык:
английский
Журнал:
J Biol Chem
Год:
2022
Тип:
Статья
Аффилированная страна:
J.jbc.2022.101584
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