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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...

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Autores principales: Ishida, Ray, Cole, Jamie, Lopez-Orozco, Joaquin, Fayad, Nawell, Felix-Lopez, Alberto, Elaish, Mohamed, Luo, Shu Yue, Julien, Olivier, Kumar, Anil, Hobman, Tom C.
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
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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.
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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
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