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Human Coronavirus NL63 nsp1 Induces ...

Hardy, Kala,

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Human Coronavirus NL63 nsp1 Induces Degradation of RNA Polymerase II to Shut Off Host Protein Synthesis /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Human Coronavirus NL63 nsp1 Induces Degradation of RNA Polymerase II to Shut Off Host Protein Synthesis // Kala Hardy.
作者:	Hardy, Kala,
面頁冊數:	1 electronic resource (136 pages)
附註:	Source: Dissertations Abstracts International, Volume: 86-01, Section: B.
Contained By:	Dissertations Abstracts International86-01B.
標題:	Virology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31335703
ISBN:	9798383198032

Human Coronavirus NL63 nsp1 Induces Degradation of RNA Polymerase II to Shut Off Host Protein Synthesis /
Hardy, Kala,

Human Coronavirus NL63 nsp1 Induces Degradation of RNA Polymerase II to Shut Off Host Protein Synthesis /Kala Hardy. - 1 electronic resource (136 pages)

Source: Dissertations Abstracts International, Volume: 86-01, Section: B.

Coronaviruses (CoVs) are an emerging public health threat that cause mild to severe respiratory infections. One major pathogenicity factor found in α- and β-CoVs is nonstructural protein 1 (nsp1), which induces general shutoff of host protein synthesis to block host antiviral responses. In β-CoVs, nsp1 is known to block mRNA translation by binding to the mRNA entry channel of ribosomes. However, how nsp1 functions in other CoVs is not fully elucidated. We compared the host shutoff activity of five human CoVs and found that nsp1 proteins from the human α-CoVs NL63 and 229E both prevented reporter gene expression, but NL63 had the strongest shutoff activity of all nsp1s tested. Interestingly, NL63 nsp1 did not bind to ribosomes or prevent mRNA translation, unlike nsp1 from the β-CoVs SARS-CoV-1 and -2. Instead, it specifically prevented transcription by RNA polymerase II (RNAPII). The domain required for this activity is located in the central part of the protein, which we found by characterizing chimeric proteins composed of nsp1 from NL63 and 229E. We further investigated the impact of NL63 nsp1 on RNAPII expression and found that NL63 nsp1 caused proteasomal degradation of Rpb1, the catalytic subunit of RNAPII, in a ubiquitin-dependent manner. This ubiquitination and degradation are specific to Rpb1 and are independent of its phosphorylation status. We also confirmed that Rpb1 was ubiquitinated and degraded in NL63 infected cells. Overall, the work presented in this thesis demonstrates that NL63 nsp1 prevents host protein expression by inducing host RNAPII degradation. This mechanism of host shutoff has not been reported for CoVs. Our study revealed that although all α- and β-CoVs express host shutoff protein nsp1, they use completely different approaches to block host responses to viral infections.

English

ISBN: 9798383198032Subjects--Topical Terms:

642304
Virology.
Subjects--Index Terms:

Coronaviruses

Human Coronavirus NL63 nsp1 Induces Degradation of RNA Polymerase II to Shut Off Host Protein Synthesis /
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520 $a Coronaviruses (CoVs) are an emerging public health threat that cause mild to severe respiratory infections. One major pathogenicity factor found in α- and β-CoVs is nonstructural protein 1 (nsp1), which induces general shutoff of host protein synthesis to block host antiviral responses. In β-CoVs, nsp1 is known to block mRNA translation by binding to the mRNA entry channel of ribosomes. However, how nsp1 functions in other CoVs is not fully elucidated. We compared the host shutoff activity of five human CoVs and found that nsp1 proteins from the human α-CoVs NL63 and 229E both prevented reporter gene expression, but NL63 had the strongest shutoff activity of all nsp1s tested. Interestingly, NL63 nsp1 did not bind to ribosomes or prevent mRNA translation, unlike nsp1 from the β-CoVs SARS-CoV-1 and -2. Instead, it specifically prevented transcription by RNA polymerase II (RNAPII). The domain required for this activity is located in the central part of the protein, which we found by characterizing chimeric proteins composed of nsp1 from NL63 and 229E. We further investigated the impact of NL63 nsp1 on RNAPII expression and found that NL63 nsp1 caused proteasomal degradation of Rpb1, the catalytic subunit of RNAPII, in a ubiquitin-dependent manner. This ubiquitination and degradation are specific to Rpb1 and are independent of its phosphorylation status. We also confirmed that Rpb1 was ubiquitinated and degraded in NL63 infected cells. Overall, the work presented in this thesis demonstrates that NL63 nsp1 prevents host protein expression by inducing host RNAPII degradation. This mechanism of host shutoff has not been reported for CoVs. Our study revealed that although all α- and β-CoVs express host shutoff protein nsp1, they use completely different approaches to block host responses to viral infections.
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