Endomembrane targeting of human OAS1 p46 augments antiviral activity
العنوان: | Endomembrane targeting of human OAS1 p46 augments antiviral activity |
---|---|
المؤلفون: | Eric J. Allenspach, Joshua J. Woodward, Nandan S. Gokhale, Jennifer L. Hyde, Karen Cerosaletti, Joseph Perez, Snehal Ozarkar, Jonathan M. Clingan, Saumendra N. Sarkar, Michael Gale, Justin A Roby, Shivam A. Zaver, Ram Savan, Alison M. Kell, Erola Pairo-Castineira, Adriana Forero, Eileen T. McAnarney, J Kenneth Baillie, Frank Soveg, Chiraag Balu, Jane H. Buckner, Uma Malhotra, Vineet D. Menachery, Cate Speake, Tien-Ying Hsiang, Daniel B. Stetson, Katharina Esser-Nobis, Johannes Schwerk, Amy E. L. Stone, Julian R. Smith |
بيانات النشر: | Cold Spring Harbor Laboratory, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Gene isoform, Flavivirus, Innate immune system, Viral replication, Picornavirus, viruses, Sense (molecular biology), RNA, Endomembrane system, Biology, biology.organism_classification, Cell biology |
الوصف: | SUMMARYMany host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from host cell innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense viral RNA generated by viruses that use these compartments for replication. Here, we reveal that an isoform of oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 p46 confers enhanced access to viral replication sites and results in increased antiviral activity against a subset of RNA viruses including flavivirus, picornavirus, and SARS-CoV-2. Finally, our human genetic analysis shows that the OAS1 splice-site SNP responsible for production of the OAS1 p46 isoform strongly associates with COVID-19 severity. This study highlights the importance of endomembrane targeting for the antiviral specificity of OAS1 and suggests early control of SARS-CoV-2 replication through OAS1-p46 is an important determinant of COVID-19 severity. |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::3b59d9d71a19dc95c6e0fb997ea77217Test https://doi.org/10.1101/2021.04.21.440697Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi...........3b59d9d71a19dc95c6e0fb997ea77217 |
قاعدة البيانات: | OpenAIRE |
ResultId |
1 |
---|---|
Header |
edsair OpenAIRE edsair.doi...........3b59d9d71a19dc95c6e0fb997ea77217 859 3 unknown 858.58740234375 |
PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsair&AN=edsair.doi...........3b59d9d71a19dc95c6e0fb997ea77217&custid=s6537998&authtype=sso |
FullText |
Array
(
[Availability] => 0
)
|
Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Endomembrane targeting of human OAS1 p46 augments antiviral activity
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Eric+J%2E+Allenspach%22">Eric J. Allenspach</searchLink><br /><searchLink fieldCode="AR" term="%22Joshua+J%2E+Woodward%22">Joshua J. Woodward</searchLink><br /><searchLink fieldCode="AR" term="%22Nandan+S%2E+Gokhale%22">Nandan S. Gokhale</searchLink><br /><searchLink fieldCode="AR" term="%22Jennifer+L%2E+Hyde%22">Jennifer L. Hyde</searchLink><br /><searchLink fieldCode="AR" term="%22Karen+Cerosaletti%22">Karen Cerosaletti</searchLink><br /><searchLink fieldCode="AR" term="%22Joseph+Perez%22">Joseph Perez</searchLink><br /><searchLink fieldCode="AR" term="%22Snehal+Ozarkar%22">Snehal Ozarkar</searchLink><br /><searchLink fieldCode="AR" term="%22Jonathan+M%2E+Clingan%22">Jonathan M. Clingan</searchLink><br /><searchLink fieldCode="AR" term="%22Saumendra+N%2E+Sarkar%22">Saumendra N. Sarkar</searchLink><br /><searchLink fieldCode="AR" term="%22Michael+Gale%22">Michael Gale</searchLink><br /><searchLink fieldCode="AR" term="%22Justin+A+Roby%22">Justin A Roby</searchLink><br /><searchLink fieldCode="AR" term="%22Shivam+A%2E+Zaver%22">Shivam A. Zaver</searchLink><br /><searchLink fieldCode="AR" term="%22Ram+Savan%22">Ram Savan</searchLink><br /><searchLink fieldCode="AR" term="%22Alison+M%2E+Kell%22">Alison M. Kell</searchLink><br /><searchLink fieldCode="AR" term="%22Erola+Pairo-Castineira%22">Erola Pairo-Castineira</searchLink><br /><searchLink fieldCode="AR" term="%22Adriana+Forero%22">Adriana Forero</searchLink><br /><searchLink fieldCode="AR" term="%22Eileen+T%2E+McAnarney%22">Eileen T. McAnarney</searchLink><br /><searchLink fieldCode="AR" term="%22J+Kenneth+Baillie%22">J Kenneth Baillie</searchLink><br /><searchLink fieldCode="AR" term="%22Frank+Soveg%22">Frank Soveg</searchLink><br /><searchLink fieldCode="AR" term="%22Chiraag+Balu%22">Chiraag Balu</searchLink><br /><searchLink fieldCode="AR" term="%22Jane+H%2E+Buckner%22">Jane H. Buckner</searchLink><br /><searchLink fieldCode="AR" term="%22Uma+Malhotra%22">Uma Malhotra</searchLink><br /><searchLink fieldCode="AR" term="%22Vineet+D%2E+Menachery%22">Vineet D. Menachery</searchLink><br /><searchLink fieldCode="AR" term="%22Cate+Speake%22">Cate Speake</searchLink><br /><searchLink fieldCode="AR" term="%22Tien-Ying+Hsiang%22">Tien-Ying Hsiang</searchLink><br /><searchLink fieldCode="AR" term="%22Daniel+B%2E+Stetson%22">Daniel B. Stetson</searchLink><br /><searchLink fieldCode="AR" term="%22Katharina+Esser-Nobis%22">Katharina Esser-Nobis</searchLink><br /><searchLink fieldCode="AR" term="%22Johannes+Schwerk%22">Johannes Schwerk</searchLink><br /><searchLink fieldCode="AR" term="%22Amy+E%2E+L%2E+Stone%22">Amy E. L. Stone</searchLink><br /><searchLink fieldCode="AR" term="%22Julian+R%2E+Smith%22">Julian R. Smith</searchLink> ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Cold Spring Harbor Laboratory, 2021. ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2021 ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22Gene+isoform%22">Gene isoform</searchLink><br /><searchLink fieldCode="DE" term="%22Flavivirus%22">Flavivirus</searchLink><br /><searchLink fieldCode="DE" term="%22Innate+immune+system%22">Innate immune system</searchLink><br /><searchLink fieldCode="DE" term="%22Viral+replication%22">Viral replication</searchLink><br /><searchLink fieldCode="DE" term="%22Picornavirus%22">Picornavirus</searchLink><br /><searchLink fieldCode="DE" term="%22viruses%22">viruses</searchLink><br /><searchLink fieldCode="DE" term="%22Sense+%28molecular+biology%29%22">Sense (molecular biology)</searchLink><br /><searchLink fieldCode="DE" term="%22RNA%22">RNA</searchLink><br /><searchLink fieldCode="DE" term="%22Endomembrane+system%22">Endomembrane system</searchLink><br /><searchLink fieldCode="DE" term="%22Biology%22">Biology</searchLink><br /><searchLink fieldCode="DE" term="%22biology%2Eorganism%5Fclassification%22">biology.organism_classification</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+biology%22">Cell biology</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => SUMMARYMany host RNA sensors are positioned in the cytosol to detect viral RNA during infection. However, most positive-strand RNA viruses replicate within a modified organelle co-opted from intracellular membranes of the endomembrane system, which shields viral products from host cell innate immune sensors. Targeting innate RNA sensors to the endomembrane system may enhance their ability to sense viral RNA generated by viruses that use these compartments for replication. Here, we reveal that an isoform of oligoadenylate synthetase 1, OAS1 p46, is prenylated and targeted to the endomembrane system. Membrane localization of OAS1 p46 confers enhanced access to viral replication sites and results in increased antiviral activity against a subset of RNA viruses including flavivirus, picornavirus, and SARS-CoV-2. Finally, our human genetic analysis shows that the OAS1 splice-site SNP responsible for production of the OAS1 p46 isoform strongly associates with COVID-19 severity. This study highlights the importance of endomembrane targeting for the antiviral specificity of OAS1 and suggests early control of SARS-CoV-2 replication through OAS1-p46 is an important determinant of COVID-19 severity. ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://explore.openaire.eu/search/publication?articleId=doi_________::3b59d9d71a19dc95c6e0fb997ea77217" linkWindow="_blank">https://explore.openaire.eu/search/publication?articleId=doi_________::3b59d9d71a19dc95c6e0fb997ea77217</link><br /><link linkTarget="URL" linkTerm="https://doi.org/10.1101/2021.04.21.440697" linkWindow="_blank">https://doi.org/10.1101/2021.04.21.440697</link> ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => OPEN ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsair.doi...........3b59d9d71a19dc95c6e0fb997ea77217 ) |
RecordInfo |
Array
(
[BibEntity] => Array
(
[Languages] => Array
(
[0] => Array
(
[Text] => Undetermined
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => Gene isoform
[Type] => general
)
[1] => Array
(
[SubjectFull] => Flavivirus
[Type] => general
)
[2] => Array
(
[SubjectFull] => Innate immune system
[Type] => general
)
[3] => Array
(
[SubjectFull] => Viral replication
[Type] => general
)
[4] => Array
(
[SubjectFull] => Picornavirus
[Type] => general
)
[5] => Array
(
[SubjectFull] => viruses
[Type] => general
)
[6] => Array
(
[SubjectFull] => Sense (molecular biology)
[Type] => general
)
[7] => Array
(
[SubjectFull] => RNA
[Type] => general
)
[8] => Array
(
[SubjectFull] => Endomembrane system
[Type] => general
)
[9] => Array
(
[SubjectFull] => Biology
[Type] => general
)
[10] => Array
(
[SubjectFull] => biology.organism_classification
[Type] => general
)
[11] => Array
(
[SubjectFull] => Cell biology
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Endomembrane targeting of human OAS1 p46 augments antiviral activity
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Eric J. Allenspach
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Joshua J. Woodward
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Nandan S. Gokhale
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jennifer L. Hyde
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Karen Cerosaletti
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Joseph Perez
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Snehal Ozarkar
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jonathan M. Clingan
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Saumendra N. Sarkar
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Michael Gale
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Justin A Roby
)
)
)
[11] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Shivam A. Zaver
)
)
)
[12] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ram Savan
)
)
)
[13] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Alison M. Kell
)
)
)
[14] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Erola Pairo-Castineira
)
)
)
[15] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Adriana Forero
)
)
)
[16] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Eileen T. McAnarney
)
)
)
[17] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => J Kenneth Baillie
)
)
)
[18] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Frank Soveg
)
)
)
[19] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Chiraag Balu
)
)
)
[20] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jane H. Buckner
)
)
)
[21] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Uma Malhotra
)
)
)
[22] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Vineet D. Menachery
)
)
)
[23] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Cate Speake
)
)
)
[24] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Tien-Ying Hsiang
)
)
)
[25] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Daniel B. Stetson
)
)
)
[26] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Katharina Esser-Nobis
)
)
)
[27] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Johannes Schwerk
)
)
)
[28] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Amy E. L. Stone
)
)
)
[29] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Julian R. Smith
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 22
[M] => 04
[Type] => published
[Y] => 2021
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-locals
[Value] => edsair
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsairFT
)
)
)
)
)
)
)
|
IllustrationInfo |