Mx GTPases: dynamin-like antiviral machines of innate immunity

• Mx proteins are key intracellular restriction factors with broad antiviral activity.
• Mx proteins have the typical three-domain architecture of dynamin-like GTPases.
• Highly variable Mx domains serve as antiviral interfaces under evolutionary pressure.
• Human MxB (MX2) is a newly identified interferon-induced restriction factor for HIV-1.
• A few amino acids of the viral nucleocapsid proteins NP and CA determine MxA (MX1) sensitivity of influenza A viruses and MxB (MX2) sensitivity of HIV-1, respectively.

The Mx dynamin-like GTPases are key antiviral effector proteins of the type I and type III interferon (IFN) systems. They inhibit several different viruses by blocking early steps of the viral replication cycle. We focus on new structural and functional insights and discuss recent data revealing that human MxA (MX1) provides a safeguard against introduction of avian influenza A viruses (FLUAV) into the human population. The related human MxB (MX2) serves as restriction factor for HIV-1 and other primate lentiviruses.