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Interfering with Interferons : = Interplay Between SARS-CoV-2 and Interferon Response.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Interfering with Interferons :/
其他題名:	Interplay Between SARS-CoV-2 and Interferon Response.
作者:	Chen, Xi.
面頁冊數:	1 online resource (45 pages)
附註:	Source: Dissertations Abstracts International, Volume: 84-11, Section: B.
Contained By:	Dissertations Abstracts International84-11B.
標題:	Tumor necrosis factor-TNF. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30450261click for full text (PQDT)
ISBN:	9798379476700

Interfering with Interferons : = Interplay Between SARS-CoV-2 and Interferon Response.
Chen, Xi.

Interfering with Interferons :Interplay Between SARS-CoV-2 and Interferon Response. - 1 online resource (45 pages)

Source: Dissertations Abstracts International, Volume: 84-11, Section: B.

Thesis (Ph.D.)--Karolinska Institutet (Sweden), 2023.

Includes bibliographical references

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused the coronavirusdisease 2019 (COVID-19) pandemic, which has been an ongoing global health crisis. At thebeginning of the pandemic, all the efforts were directed toward understanding the pathogenesisof the virus. An early interferon (IFN) response is crucial in initiating and boosting the antiviralresponse. It was identified that the IFN response is dim and delayed in COVID-19 patients,accompanied by pro-inflammatory cytokine production. Circumvention and dysregulation ofinterferon (IFN) response were found to be characteristic of the SARS-CoV-2 infection,leading to its pathogenicity and severity in a group of COVID-19 patients. Thus, a betterunderstanding of the pathogenic mechanisms of SARS-CoV-2 infection is crucial for a bettertherapeutic strategy against the disease. The thesis aimed to characterize the interplay betweenSARS-CoV-2 and host IFN response.In Paper I, we assessed the susceptibility and cytotoxicity of the first Swedish isolate of SARSCoV-2 in six cell lines of human origin in comparison to other globally isolated strains.Furthermore, we determined the proteomic landscape during SARS-CoV-2 infection in thesusceptible cell lines, using LC-MS/MS-based tandem mass tags (TMT) labeling quantitativeproteomics technology. The studies provided an overview of the signaling pathways altered bythe SARS-CoV-2, elucidating IFN-signaling pathways.In Paper II, we identified and characterized the expression of antiviral ISGs during SARSCoV-1, MERS-CoV, and SARS-CoV-2 infection of the Huh7 cell line using TMT-labeled LCMS/MS. Transcriptomic ISG signatures were identified for SARS-CoV-2 in a time-dependentmanner. Furthermore, we identified that SARS-CoV-2 inhibited IFN-b production and showeda muted and delayed activation of ISGs in Huh7 cells. IFN treatment was found to be effectivein controlling the virus prior to the establishment of the infection, and IFN treatment postinfectionhad no effect on the virus. We also showed increased virus production in a senescentHuh cell model.Paper III explored how the virus infection impacts the IFN signaling pathways (IFN-I/ IFNIII)and interferon-stimulated gene (ISG) expression in COVID-19 patients. Irrespective of thedisease status, heterogeneity was observed in the expression of ISGs. We categorized thepatients based on type-I, type-II, and antiviral-response-related ISG scores obtained fromwhole-blood transcriptomics data. We investigated factors like immune cell proportions,neutrophil extracellular traps (NETs), inflammatory factors, metabolic status, andautoimmunity against IFNs, to try to find any association with the ISG score status of thepatients. Autoimmune antibodies against IFNs were more prominent in patients with low ISGscores. Furthermore, the expression of ISGs was associated with a perturbation in amino acidand lipid metabolism.In Paper IV, we investigated a potential innate immune evasion mechanism by SARS-CoV-2. We studied the role of a crucial virus protease: papain-like protease (PLpro), which has apotent deubiquitinating and deISGylating activity in inhibiting type-I IFN response. Usingimmunoprecipitation, we have identified that SARS-CoV-2 interacts with RIG-I signalosomecomponents TRIM25 and RIG-I. Catalytically active PLpro could deubiquitinate theconstitutively active 2CARD domain, which leads to the inhibition of interferon response. TheSARS-CoV-2 homologs in other coronaviruses also interacted with TRIM25 and RIG-I andinhibited IFN production. These findings show another innate immune regulatory mechanismby Ub/UbL deconjugated activity of coronavirus PLpro.In summary, the research covered in this thesis deciphers the significance of interferon responseduring SARS-CoV-2 infection.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798379476700Subjects--Topical Terms:

3560383
Tumor necrosis factor-TNF.
Index Terms--Genre/Form:

542853
Electronic books.

Interfering with Interferons : = Interplay Between SARS-CoV-2 and Interferon Response.
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