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Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus.

ABSTRACT: 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-E3L?37N) has been shown to be attenuated in mouse models, and infection with VACV-E3L?37N 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-E3L?37N. 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.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.

SUBMITTER: Arndt WD

PROVIDER: S-EPMC4580173 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus.

Arndt William D WD Cotsmire Samantha S Trainor Kelly K Harrington Heather H Hauns Kevin K Kibler Karen V KV Huynh Trung P TP Jacobs Bertram L BL

Journal of virology 20150805 20

<h4>Unlabelled</h4>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 geno ...[more]

PMID: 26246580

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Dataset Information

Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus.

Publications

Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus.

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