Authors

D Allred¹;  ¹ University of Florida, United States

Discussion

Tick-borne intraerythrocytic parasites of the genus Babesia are notoriously effective at establishing infections of extreme duration. Cytoadhesion and rapid structural and antigenic variation of the cytoadhesion ligand, two known processes contributing to this success, are both embodied in the heterodimeric protein, VESA1. VESA1 subunits are encoded by separate branches of the ves multigene family and expressed in a monoparalogous manner. The vesfamily is present in a highly amplified and diversified form among all Babesia sensu stricto parasites observed to date, but is largely absent from species outside this group. Sudden wholesale changes in expressed vessequences may occur through in situ transcriptional switching (isTS) among ves family members. Lacking specific binding domains like those found in the analogous PfEMP1 proteins of Plasmodium falciparum, novel adhesive VESA1 isoforms must be generated de novo. This appears to occur through the random recombination events of segmental gene conversion (SGC), with simultaneous generation of hugely diverse antigenic variants. The enzymatic mediators of this process have not yet been identified. While resembling homologous recombination (HR), SGC is undeterred by knockout of the lone rad51 gene, rendering HR unlikely as a major pathway. Functional knockout of the translesion Rev1/Pol repair pathway renders parasites highly sensitive to DNA base damage but does not appear to significantly impact SGC (analysis ongoing), suggesting that frequent template-switching also is not responsible. Triggers of the DNA breaks leading to SGC are not known, but occur spontaneously and must target the vesfamily specifically. We hypothesize this may be related to the extreme enrichment of the vesmultigene family with oxidation-sensitive G-quadruplex sequences. These disparate points will be contrasted between Babesiaand other parasite species. Supported by NIAID, American Heart Association, USDA, USAID, University of Florida.