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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

Authors :
Ray Ishida
Jamie Cole
Joaquin Lopez-Orozco
Nawell Fayad
Alberto Felix-Lopez
Mohamed Elaish
Shu Yue Luo
Olivier Julien
Anil Kumar
Tom C. Hobman
Source :
Cells, Cells; Volume 10; Issue 12; Pages: 3510, Cells, Vol 10, Iss 3510, p 3510 (2021)
Publication Year :
2021
Publisher :
MDPI, 2021.

Abstract

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.

Details

Language :
English
ISSN :
20734409
Volume :
10
Issue :
12
Database :
OpenAIRE
Journal :
Cells
Accession number :
edsair.doi.dedup.....ff00c1593cadd8c09408f72ea4643eb2