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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
- 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.
- Subjects :
- TFIIE2
Transcription, Genetic
QH301-705.5
viruses
Down-Regulation
Alphavirus
Viral Nonstructural Proteins
MAYV
Article
Rpb1
Cell Line
03 medical and health sciences
Transcription Factors, TFII
Animals
Humans
Biology (General)
alphavirus
nsP2
interferon
030304 developmental biology
Cell Nucleus
0303 health sciences
030306 microbiology
virus diseases
General Medicine
biochemical phenomena, metabolism, and nutrition
3. Good health
Protein Subunits
Protein Transport
Host-Pathogen Interactions
Interferon Regulatory Factor-3
Interferons
RNA Polymerase II
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 10
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....ff00c1593cadd8c09408f72ea4643eb2