Cargando…
Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2
Mayaro virus (MAYV) is an emerging mosquito-transmitted virus that belongs to the genus Alphavirus within the family Togaviridae. Humans infected with MAYV often develop chronic and debilitating arthralgia and myalgia. The virus is primarily maintained via a sylvatic cycle, but it has the potential...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700540/ https://www.ncbi.nlm.nih.gov/pubmed/34944018 http://dx.doi.org/10.3390/cells10123510 |
_version_ | 1784620781562494976 |
---|---|
author | Ishida, Ray Cole, Jamie Lopez-Orozco, Joaquin Fayad, Nawell Felix-Lopez, Alberto Elaish, Mohamed Luo, Shu Yue Julien, Olivier Kumar, Anil Hobman, Tom C. |
author_facet | Ishida, Ray Cole, Jamie Lopez-Orozco, Joaquin Fayad, Nawell Felix-Lopez, Alberto Elaish, Mohamed Luo, Shu Yue Julien, Olivier Kumar, Anil Hobman, Tom C. |
author_sort | Ishida, Ray |
collection | PubMed |
description | Mayaro virus (MAYV) is an emerging mosquito-transmitted virus that belongs to the genus Alphavirus within the family Togaviridae. Humans infected with MAYV often develop chronic and debilitating arthralgia and myalgia. The virus is primarily maintained via a sylvatic cycle, but it has the potential to adapt to urban settings, which could lead to large outbreaks. The interferon (IFN) system is a critical antiviral response that limits replication and pathogenesis of many different RNA viruses, including alphaviruses. Here, we investigated how MAYV infection affects the induction phase of the IFN response. Production of type I and III IFNs was efficiently suppressed during MAYV infection, and mapping revealed that expression of the viral non-structural protein 2 (nsP2) was sufficient for this process. Interactome analysis showed that nsP2 interacts with DNA-directed RNA polymerase II subunit A (Rpb1) and transcription initiation factor IIE subunit 2 (TFIIE2), which are host proteins required for RNA polymerase II-mediated transcription. Levels of these host proteins were reduced by nsP2 expression and during infection by MAYV and related alphaviruses, suggesting that nsP2-mediated inhibition of host cell transcription is an important aspect of how some alphaviruses block IFN induction. The findings from this study may prove useful in design of vaccines and antivirals, which are currently not available for protection against MAYV and infection by other alphaviruses. |
format | Online Article Text |
id | pubmed-8700540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87005402021-12-24 Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2 Ishida, Ray Cole, Jamie Lopez-Orozco, Joaquin Fayad, Nawell Felix-Lopez, Alberto Elaish, Mohamed Luo, Shu Yue Julien, Olivier Kumar, Anil Hobman, Tom C. Cells Article Mayaro virus (MAYV) is an emerging mosquito-transmitted virus that belongs to the genus Alphavirus within the family Togaviridae. Humans infected with MAYV often develop chronic and debilitating arthralgia and myalgia. The virus is primarily maintained via a sylvatic cycle, but it has the potential to adapt to urban settings, which could lead to large outbreaks. The interferon (IFN) system is a critical antiviral response that limits replication and pathogenesis of many different RNA viruses, including alphaviruses. Here, we investigated how MAYV infection affects the induction phase of the IFN response. Production of type I and III IFNs was efficiently suppressed during MAYV infection, and mapping revealed that expression of the viral non-structural protein 2 (nsP2) was sufficient for this process. Interactome analysis showed that nsP2 interacts with DNA-directed RNA polymerase II subunit A (Rpb1) and transcription initiation factor IIE subunit 2 (TFIIE2), which are host proteins required for RNA polymerase II-mediated transcription. Levels of these host proteins were reduced by nsP2 expression and during infection by MAYV and related alphaviruses, suggesting that nsP2-mediated inhibition of host cell transcription is an important aspect of how some alphaviruses block IFN induction. The findings from this study may prove useful in design of vaccines and antivirals, which are currently not available for protection against MAYV and infection by other alphaviruses. MDPI 2021-12-12 /pmc/articles/PMC8700540/ /pubmed/34944018 http://dx.doi.org/10.3390/cells10123510 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ishida, Ray Cole, Jamie Lopez-Orozco, Joaquin Fayad, Nawell Felix-Lopez, Alberto Elaish, Mohamed Luo, Shu Yue Julien, Olivier Kumar, Anil Hobman, Tom C. Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2 |
title | Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2 |
title_full | Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2 |
title_fullStr | Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2 |
title_full_unstemmed | Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2 |
title_short | Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2 |
title_sort | mayaro virus non-structural protein 2 circumvents the induction of interferon in part by depleting host transcription initiation factor iie subunit 2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700540/ https://www.ncbi.nlm.nih.gov/pubmed/34944018 http://dx.doi.org/10.3390/cells10123510 |
work_keys_str_mv | AT ishidaray mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT colejamie mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT lopezorozcojoaquin mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT fayadnawell mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT felixlopezalberto mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT elaishmohamed mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT luoshuyue mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT julienolivier mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT kumaranil mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 AT hobmantomc mayarovirusnonstructuralprotein2circumventstheinductionofinterferoninpartbydepletinghosttranscriptioninitiationfactoriiesubunit2 |