Assay and functional analysis of dynamin-like Mx proteins
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Published on: January 11, 2017
Georg Kochs1, Mike Reichelt, Dganit Danino
1Department of Virology, University of Freiburg, Germany.
Abstract:
Mx proteins are interferon-induced large guanosine triphosphatases (GTPases) that share structural and functional properties with dynamin and dynamin-like proteins, such as self-assembly and association with intracellular membranes. A unique property of some Mx proteins is their antiviral activity against a range of RNA viruses, including influenza viruses and members of the bunyavirus family. These viruses are inhibited at an early stage in their life cycle, soon after host cell entry and before genome amplification. The association of the human MxA GTPase with membranes of the endoplasmic reticulum seems to support its antiviral function by providing an interaction platform that facilitates viral target recognition, MxA oligomerization, and missorting of the resulting multiprotein complex into large intracellular aggregates.
Insights
Mx proteins, or interferon-induced guanosine triphosphatases (GTPases), exhibit antiviral properties by inhibiting RNA viruses like influenza early in their life cycle. Human MxA GTPase utilizes endoplasmic reticulum membranes for viral target recognition and aggregate formation, crucial for its antiviral function.
Area of Science:
- Molecular Biology
- Virology
- Immunology
Background:
- Mx proteins are interferon-induced guanosine triphosphatases (GTPases) with dynamin-like properties.
- They exhibit self-assembly and associate with intracellular membranes.
- Some Mx proteins possess antiviral activity against RNA viruses, including influenza and bunyaviruses.
Purpose of the Study:
- To elucidate the mechanism of antiviral activity of Mx proteins, specifically human MxA.
- To understand the role of intracellular membranes in Mx protein function.
- To investigate the interaction of MxA with viral targets and its oligomerization process.
Main Methods:
- Analysis of Mx protein structure and function.
- Studies on MxA association with endoplasmic reticulum membranes.
- Investigation of MxA's role in viral life cycle inhibition.
Main Results:
- Mx proteins inhibit RNA viruses early in their life cycle, post-entry and pre-amplification.
- Human MxA GTPase associates with endoplasmic reticulum membranes.
- This membrane association facilitates MxA oligomerization, viral target recognition, and formation of intracellular aggregates.
Conclusions:
- The antiviral mechanism of MxA involves membrane association, oligomerization, and aggregate formation.
- Endoplasmic reticulum membranes serve as platforms for MxA's antiviral activity.
- MxA's function is critical for inhibiting viral replication through missorting and aggregation.

