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.

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.

Related Concept Videos

Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.2K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.2K
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
45.8K
Viral Structure00:56

Viral Structure

Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
62.0K
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.8K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K