Dokumentdetails
ID
oai:HAL:hal-03937465v1
Thema
MX1 restriction factor influenza A virus interferon bunyavirus rhabdovirus [SDV.BBM.BS]Life Sciences [q-bio]/... [SDV.MP.VIR]Life Sciences [q-bio]/...Autor
Mckellar, Joe Arnaud-Arnould, Mary Chaloin, Laurent Tauziet, Marine Arpin-André, Charlotte Pourcelot, Oriane Blaise, Mickaël Moncorgé, Olivier Goujon, CarolineLangue
enEditor
HAL CCSD;American Society for Biochemistry and Molecular Biology
Kategorie
CNRS - Centre national de la recherche scientifique
Jahr
2023
Auflistungsdatum
07.10.2023
Schlüsselwörter
viruses gtpase influenza hsmx1 protein region leucine conserved mx1 activity antiviral domainZusammenfassung
International audience; Myxovirus resistance protein 1 (MX1) and MX2 are homologous, dynamin-like large GTPases, induced upon interferon exposure.
Human MX1 (HsMX1) is known to inhibit many viruses, including influenza A virus, by likely acting at various steps of their life cycles.
Despite decades of studies, the mechanism(s) of action with which MX1 proteins manage to inhibit target viruses is not fully understood.
MX1 proteins are mechano-enzymes and share a similar organization to dynamin, with a GTPase domain and a carboxy-terminal stalk domain, connected by a bundle signaling element.
These three elements are known to be essential for antiviral activity.
HsMX1 has two unstructured regions, the L4 loop, also essential for antiviral activity, and a short amino (N)-terminal region, which greatly varies between MX1 proteins of different species.
The role of this N-terminal domain in antiviral activity is not known.
Herein, using mutagenesis, imaging, and biochemical approaches, we demonstrate that the N-terminal domain of HsMX1 is essential for antiviral activity against influenza A virus, Vesicular Stomatitis Virus, and La Crosse virus.
Furthermore, we pinpoint a highly conserved leucine within this region, which is absolutely crucial for human, mouse, and bat MX1 protein antiviral activity.
Importantly, mutation of this leucine does not compromise GTPase activity or oligomerization capabilities but does modify MX1 protein subcellular localization.
The discovery of this essential and highly conserved residue defines this region as key for antiviral activity and may reveal insights as to the mechanism(s) of action of MX1 proteins.
Mckellar, Joe,Arnaud-Arnould, Mary,Chaloin, Laurent,Tauziet, Marine,Arpin-André, Charlotte,Pourcelot, Oriane,Blaise, Mickaël,Moncorgé, Olivier,Goujon, Caroline, 2023, An evolutionarily conserved N-terminal leucine is essential for MX1 GTPase antiviral activity against different families of RNA viruses, HAL CCSD;American Society for Biochemistry and Molecular Biology
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