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6th Edition of World Congress on Infectious Diseases

June 24-26, 2024 | Paris, France

June 24 -26, 2024 | Paris, France
Infection 2024

Yen Chin Liu

Speaker at Infectious Diseases Conferences - Yen Chin Liu
Chang Gung University, Taiwan
Title : SARS-CoV-2 omicron nucleocapsid effectively suppresses interferon beta expression via interaction with host HSPA4

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can dysregulate host antiviral responses, including interferon production, to facilitate viral replication and spread via interacting with their hosts; however, the impact of the SARS-CoV-2 Omicron nucleocapsid protein on the innate immune response remains unclear. In this study, FLAG-tagged nucleocapsids of SARS-CoV-2 were first overexpressed in HEK293T cells, after which anti-FLAG immunoprecipitation and Western blotting assays were performed. Nucleocapsid-associated protein complexes in human cells were identified using co-immunoprecipitation and were combined with in-gel digestion and ultra-high-pressure liquid chromatography coupled to tandem mass spectrometry. We discovered that the nucleocapsid of SARS-CoV-2 could specifically interact with cellular heat shock protein family A member 4 (HSPA4) in the cytoplasm. The nucleocapsid of the SARS-CoV-2 Omicron variant exhibited a heightened interaction with HSPA4 compared to other variants. Downregulation of HSPA4 expression in A549-ACE2-TMPRSS2 cells decreased the innate immune responses and significantly increased the viral titers, suggesting that HSPA4 was an antiviral regulator in the SARS-CoV-2 life cycle. We further demonstrated that the nucleocapsid inhibited the phosphorylated-interferon regulatory factor 3 protein, interferon beta mRNA, and interferon-stimulated genes; however, HSPA4 overexpression could recover them. Moreover, HSPA4 is involved in the upregulation of innate antiviral immunity. Our data suggests a novel mechanism by which the SARS-CoV-2 nucleocapsid hijacks cellular HSPA4 to suppress the host innate immune response and facilitate viral replication.

Biography:

Dr. Yen-Chin Liu received her PhD degree in 2014 from Graduate Institute of Biomedical Sciences, Chang Gung University, Taiwan. The findings reveal a novel mechanism of viruses attacking hosts whereby picornaviral polymerase (3Dpol) enters the nucleus and targets the central pre-mRNA processing factor 8 (Prp8) to block pre-mRNA splicing and mRNA synthesis. This work has been published in PLoS Pathogens.
Dr. Liu worked as post-doctoral fellow from 2014 to 2019 in Department of Microbiology, the University of Hong Kong. She identified a novel virus host interaction mediated by XRN1 in influenza virus infection. This work has been accepted by mBio.

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