Description:
<jats:title>Abstract</jats:title><jats:p>Some strains of the protozoan parasite<jats:italic>Toxoplasma gondii</jats:italic>(such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent<jats:italic>T. gondii</jats:italic>strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1<jats:sub>CIM</jats:sub>to the<jats:italic>T. gondii</jats:italic>virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American<jats:italic>T. gondii</jats:italic>strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1<jats:sub>CIM</jats:sub>, indicating co-adaptation of host cell resistance GTPases and<jats:italic>T. gondii</jats:italic>virulence effectors.</jats:p>