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Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
Antiviral Mx proteins have an ancient origin and widespread distribution among eukaryotes
Caroline A Langley1,2,3, Peter A Dietzen1,2,3, Michael Emerman2,3
1Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA.
Abstract:
First identified in mammals, Mx proteins are potent antivirals against a broad swathe of viruses. Mx proteins arose within the Dynamin superfamily of proteins (DSP), mediating critical cellular processes, such as endocytosis and mitochondrial, plastid, and peroxisomal dynamics. And yet, the evolutionary origins of Mx proteins are poorly understood. Using a series of phylogenomic analyses with stepwise increments in taxonomic coverage, we show that Mx proteins predate the interferon signaling system in vertebrates. Our analyses find an ancient monophyletic DSP lineage in eukaryotes that groups vertebrate and invertebrate Mx proteins with previously undescribed fungal MxF proteins, the relatively uncharacterized plant and algal Dynamin 4A/4C proteins, and representatives from several early-branching eukaryotic lineages. Thus, Mx-like proteins date back close to the origin of Eukarya. Our phylogenetic analyses also reveal that host-encoded and NCLDV (nucleocytoplasmic large DNA viruses)-encoded DSPs are interspersed in four distinct DSP lineages, indicating recurrent viral theft of host DSPs. Our analyses thus reveal an ancient history of viral and antiviral functions encoded by the Dynamin superfamily in eukaryotes.
Insights
Mx proteins, ancient antivirals within the Dynamin superfamily, originated before vertebrate interferon systems. These proteins have deep evolutionary roots, predating the origin of Eukarya and showing a history of viral interactions.
Area of Science:
- Evolutionary biology
- Virology
- Cellular dynamics
Background:
- Mx proteins are potent broad-spectrum antivirals identified in mammals.
- They belong to the Dynamin superfamily of proteins (DSP), involved in crucial cellular processes.
- The evolutionary origins and ancient functions of Mx proteins remain largely unknown.
Purpose of the Study:
- To investigate the evolutionary origins of Mx proteins.
- To determine the phylogenetic relationship of Mx proteins within the Dynamin superfamily.
- To understand the ancient history of viral and antiviral functions within the DSP.
Main Methods:
- Phylogenomic analyses with increasing taxonomic scope.
- Phylogenetic reconstructions of the Dynamin superfamily.
- Comparative analysis of host- and virus-encoded DSPs.
Main Results:
- Mx proteins predate the vertebrate interferon signaling system.
- An ancient monophyletic DSP lineage includes vertebrate/invertebrate Mx, fungal MxF, and plant/algal Dynamin 4A/4C proteins.
- Mx-like proteins trace back to the origin of Eukarya.
- Evidence of recurrent viral gene theft within the DSP, with host and NCLDV-encoded DSPs interspersed in four lineages.
Conclusions:
- Mx proteins have ancient origins, dating back to the dawn of Eukarya.
- The Dynamin superfamily has a long history of encoding both host antiviral functions and being subject to viral theft.
- Understanding DSP evolution provides insights into host-pathogen interactions over deep evolutionary time.
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