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Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus.
- Source :
-
Journal of virology [J Virol] 2015 Oct; Vol. 89 (20), pp. 10489-99. Date of Electronic Publication: 2015 Aug 05. - Publication Year :
- 2015
-
Abstract
- Unlabelled: The vaccinia virus (VACV) E3 protein has been shown to be important for blocking activation of the cellular innate immune system and allowing viral replication to occur unhindered. Mutation or deletion of E3L severely affects viral host range and pathogenesis. While the monkeypox virus (MPXV) genome encodes a homologue of the VACV E3 protein, encoded by the F3L gene, the MPXV gene is predicted to encode a protein with a truncation of 37 N-terminal amino acids. VACV with a genome encoding a similarly truncated E3L protein (VACV-E3LΔ37N) has been shown to be attenuated in mouse models, and infection with VACV-E3LΔ37N has been shown to lead to activation of the host antiviral protein kinase R pathway. In this report, we present data demonstrating that, despite containing a truncated E3 homologue, MPXV phenotypically resembles a wild-type (wt) VACV rather than VACV-E3LΔ37N. Thus, MPXV appears to contain a gene or genes that can suppress the phenotypes associated with an N-terminal truncation in E3. The suppression maps to sequences outside F3L, suggesting that the suppression is extragenic in nature. Thus, MPXV appears to have evolved mechanisms to minimize the effects of partial inactivation of its E3 homologue.<br />Importance: Poxviruses have evolved to have many mechanisms to evade host antiviral innate immunity; these mechanisms may allow these viruses to cause disease. Within the family of poxviruses, variola virus (which causes smallpox) is the most pathogenic, while monkeypox virus is intermediate in pathogenicity between vaccinia virus and variola virus. Understanding the mechanisms of monkeypox virus innate immune evasion will help us to understand the evolution of poxvirus innate immune evasion capabilities, providing a better understanding of how poxviruses cause disease.<br /> (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Biological Evolution
Cell Line
Chlorocebus aethiops
Cricetulus
Epithelial Cells immunology
Epithelial Cells virology
Gene Expression
HeLa Cells
Host Specificity
Host-Pathogen Interactions
Humans
Interferon Type I genetics
Molecular Sequence Data
Monkeypox virus immunology
Monkeypox virus pathogenicity
RNA-Binding Proteins chemistry
RNA-Binding Proteins immunology
Rabbits
Sequence Alignment
Signal Transduction
Vaccinia virus immunology
Vaccinia virus pathogenicity
Vero Cells
Viral Proteins chemistry
Viral Proteins immunology
Virus Replication
Immune Evasion
Immunity, Innate
Interferon Type I immunology
Monkeypox virus genetics
RNA-Binding Proteins genetics
Vaccinia virus genetics
Viral Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 89
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 26246580
- Full Text :
- https://doi.org/10.1128/JVI.00304-15