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

Arpita Mukherjee1, Mahadeb Lo1, Pritam Chandra1

  • 1Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme-XM, Beliaghata, Kolkata, West Bengal, 700010, India.

Virology Journal
|August 12, 2024
PubMed
Abstract

Insights

Histone deacetylase 6 (HDAC6) promotes SARS-CoV-2 replication by deacetylating the viral N protein, disrupting stress granules. Inhibiting HDAC6 reduces viral load, suggesting it as an antiviral target.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, necessitates understanding host-virus interactions to find antiviral targets.
  • Identifying host factors that influence severe disease is crucial for pandemic preparedness.

Purpose of the Study:

  • To investigate the role of histone deacetylase 6 (HDAC6) in regulating SARS-CoV-2 infection.
  • To elucidate the molecular mechanisms by which HDAC6 influences viral replication and host cell response.

Main Methods:

  • Analysis of HDAC6 expression in SARS-CoV-2-infected cell lines.
  • Investigating the interaction between HDAC6, SARS-CoV-2 nucleocapsid (N) protein, and G3BP1.
  • Utilizing shRNA and specific inhibitors (tubacin) to downregulate HDAC6 activity.
  • Assessing the impact of HDAC6 modulation on viral replication.

Main Results:

  • HDAC6 expression increased upon SARS-CoV-2 infection, upregulated by the viral N protein.
  • Downregulation of HDAC6 reduced viral replication, indicating a proviral role for its deacetylase activity.
  • HDAC6 interacts with G3BP1 and the SARS-CoV-2 N protein.
  • HDAC6-mediated deacetylation of the N protein is essential for its association with G3BP1.

Conclusions:

  • HDAC6 plays a significant role in SARS-CoV-2 infection by facilitating viral replication.
  • The study reveals HDAC6's involvement in disrupting cytoplasmic stress granules via N protein deacetylation.
  • HDAC6 emerges as a potential therapeutic target for COVID-19 treatment.
Keywords:
DeacetylationG3BP1HDAC6SARS-CoV-2Stress granules (SGs)

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