ArticleJournal of virology2012
The vaccinia virus O1 protein is required for sustained activation of extracellular signal-regulated kinase 1/2 and promotes viral virulence.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 57 citations in OpenAlex.
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- Zoonotic and Zooanthroponotic Potential of Monkeypox.Advances in experimental medicine and biology · 2024Review
- Tumor Tropism of DNA Viruses for Oncolytic Virotherapy.Viruses · 2023Review
- Transcriptome Changes in Glioma Cells upon Infection with the Oncolytic Virus VV-GMCSF-Lact.Cells · 2023Article
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- Analysis of variola virus molecular evolution suggests an old origin of the virus consistent with historical records.Microbial genomics · 2023Article
- Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus.PLoS pathogens · 2021Article
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- Oncolytic vaccinia virus induces a novel phenotype of CD8Molecular therapy oncolytics · 2021Article
- Upregulation of DUSP6 impairs infectious bronchitis virus replication by negatively regulating ERK pathway and promoting apoptosis.Veterinary research · 2021Article
- Monkeypox virus emergence in wild chimpanzees reveals distinct clinical outcomes and viral diversity.Nature microbiology · 2020Article
- Human DNA Virus Exploitation of the MAPK-ERK Cascade.International journal of molecular sciences · 2019Review
- Punctuated Evolution of Myxoma Virus: Rapid and Disjunct Evolution of a Recent Viral Lineage in Australia.Journal of virology · 2019Article
- Vaccinia virus hijacks EGFR signalling to enhance virus spread through rapid and directed infected cell motility.Nature microbiology · 2019Article
- Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?Viruses · 2017Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sustained activation of the Raf/MEK/extracellular signal-regulated kinase (ERK) pathway in infected cells has been shown to be crucial for full replication efficiency of orthopoxviruses in cell culture. In infected cells, this pathway is mainly activated by the vaccinia virus growth factor (VGF), an epidermal growth factor (EGF)-like protein. We show here that chorioallantois vaccinia virus Ankara (CVA), but not modified vaccinia virus Ankara (MVA), induced sustained activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in infected human 293 cells, although both viruses direct secretion of functional VGF. A CVA mutant lacking the O1L gene (CVA-ΔO1L) demonstrated that the O1 protein was required for sustained upregulation of the ERK1/2 pathway in 293 cells as well as in other mammalian cell lines. The highly conserved orthopoxvirus O1L gene encodes a predicted 78-kDa protein with a hitherto-unknown function. CVA-ΔO1L showed reduced plaque size and an attenuated cytopathic effect (CPE) in infected cell cultures and reduced virulence and spread from lungs to ovaries in intranasally infected BALB/c mice. Reinsertion of an intact O1L gene into MVA, which in its original form harbors a fragmented O1L open reading frame (ORF), restored ERK1/2 activation in 293 cells but did not increase replication and spread of MVA in human or other mammalian cell lines. Thus, the O1 protein was crucial for sustained ERK1/2 activation in CVA- and MVA-infected human cells, complementing the autocrine function of VGF, and enhanced virulence in vivo.
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