Evasion of the innate immune type I interferon system by Monkeypox virus

William D. Arndt, Samantha Cotsmire, Kelly Trainor, Heather Harrington, Kevin Hauns, Karen Kibler, Trung P. Huynh, Bertram Jacobs

Research output: Contribution to journalArticle

5 Citations (Scopus)

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-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.

Original languageEnglish (US)
Pages (from-to)10489-10499
Number of pages11
JournalJournal of Virology
Volume89
Issue number20
DOIs
StatePublished - 2015

Fingerprint

Monkeypox virus
Interferon Type I
Vaccinia virus
interferons
Interferon-gamma
Genes
Genome
Sequence Deletion
Host Specificity
genes
proteins
antiviral proteins
Protein Kinases
Antiviral Agents
Immune System
genome
virus replication
host range
protein kinases
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Evasion of the innate immune type I interferon system by Monkeypox virus. / Arndt, William D.; Cotsmire, Samantha; Trainor, Kelly; Harrington, Heather; Hauns, Kevin; Kibler, Karen; Huynh, Trung P.; Jacobs, Bertram.

In: Journal of Virology, Vol. 89, No. 20, 2015, p. 10489-10499.

Research output: Contribution to journalArticle

Arndt, WD, Cotsmire, S, Trainor, K, Harrington, H, Hauns, K, Kibler, K, Huynh, TP & Jacobs, B 2015, 'Evasion of the innate immune type I interferon system by Monkeypox virus', Journal of Virology, vol. 89, no. 20, pp. 10489-10499. https://doi.org/10.1128/JVI.00304-15
Arndt, William D. ; Cotsmire, Samantha ; Trainor, Kelly ; Harrington, Heather ; Hauns, Kevin ; Kibler, Karen ; Huynh, Trung P. ; Jacobs, Bertram. / Evasion of the innate immune type I interferon system by Monkeypox virus. In: Journal of Virology. 2015 ; Vol. 89, No. 20. pp. 10489-10499.
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