SARS-CoV-2 nucleocapsid protein promotes self-deacetylation by inducing HDAC6 to facilitate viral replication.

IF 4 3区医学 Q2 VIROLOGY

Virology Journal Pub Date : 2024-08-12 DOI:10.1186/s12985-024-02460-5

Arpita Mukherjee, Mahadeb Lo, Pritam Chandra, Ratul Datta Chaudhuri, Papiya De, Shanta Dutta, Mamta Chawla-Sarkar

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引用次数: 0

Abstract

Background: The global outbreak of COVID-19 caused by the SARS-CoV-2 has led to millions of deaths. This unanticipated emergency has prompted virologists across the globe to delve deeper into the intricate dynamicity of the host-virus interface with an aim to identify antiviral targets and elucidate host and viral determinants of severe disease.

Aim: The present study was undertaken to analyse the role of histone deacetylase 6 (HDAC6) in regulating SARS-CoV-2 infection.

Results: Gradual increase in HDAC6 expression was observed in different SARS-CoV-2-permissive cell lines following SARS-CoV-2 infection. The SARS-CoV-2 nucleocapsid protein (N protein) was identified as the primary viral factor responsible for upregulating HDAC6 expression. Downregulation of HDAC6 using shRNA or a specific inhibitor tubacin resulted in reduced viral replication suggesting proviral role of its deacetylase activity. Further investigations uncovered the interaction of HDAC6 with stress granule protein G3BP1 and N protein during infection. HDAC6-mediated deacetylation of SARS-CoV-2 N protein was found to be crucial for its association with G3BP1.

Conclusion: This study provides valuable insights into the molecular mechanisms underlying the disruption of cytoplasmic stress granules during SARS-CoV-2 infection and highlights the significance of HDAC6 in the process.

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SARS-CoV-2 核苷酸蛋白通过诱导 HDAC6 促进自我去乙酰化，从而促进病毒复制。

背景：由 SARS-CoV-2 引起的 COVID-19 全球爆发已导致数百万人死亡。目的：本研究旨在分析组蛋白去乙酰化酶 6 (HDAC6) 在调节 SARS-CoV-2 感染中的作用：结果：SARS-CoV-2感染后，在不同的SARS-CoV-2易感细胞系中观察到HDAC6表达逐渐增加。SARS-CoV-2核壳蛋白（N蛋白）被确定为上调HDAC6表达的主要病毒因子。使用 shRNA 或特异性抑制剂 tubacin 下调 HDAC6 可减少病毒复制，这表明 HDAC6 的去乙酰化酶活性具有挑衅性作用。进一步研究发现，在感染过程中，HDAC6 与应激颗粒蛋白 G3BP1 和 N 蛋白相互作用。研究发现，HDAC6 介导的 SARS-CoV-2 N 蛋白去乙酰化对其与 G3BP1 的结合至关重要：本研究为了解 SARS-CoV-2 感染过程中细胞质应激颗粒破坏的分子机制提供了有价值的见解，并强调了 HDAC6 在这一过程中的重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virology Journal 医学-病毒学

CiteScore

7.40

自引率

2.10%

发文量

186

审稿时长

1 months

期刊介绍： Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.