Invasion of the erythrocyte by the merozoites of the malaria parasite is a
complex process involving a range of receptor-ligand interactions. Two protein
families termed Erythrocyte Binding Like (EBL) proteins and Reticulocyte Binding
Protein Homologues (RH) play an important role in host cell recognition by the
merozoite. In the rodent malaria parasite, Plasmodium yoelii,
the 235 kDa rhoptry proteins (Py235) are coded for by a multigene family and are
members of the RH. In P. yoelii Py235 as well as a single
member of EBL have been shown to be key mediators of virulence enabling the
parasite to invade a wider range of host erythrocytes. One member of Py235,
PY01365 is most abundantly transcribed in parasite
populations and the protein specifically binds to erythrocytes and is recognized
by the protective monoclonal antibody 25.77, suggesting a key role of this
particular member in virulence. Recent studies have indicated that overall
levels of Py235 expression are essential for parasite virulence. Here we show
that disruption of PY01365 in the virulent YM line directly
impacts parasite virulence. Furthermore the disruption of
PY01365 leads to a reduction in the number of schizonts
that express members of Py235 that react specifically with the mcAb 25.77.
Erythrocyte binding assays show reduced binding of Py235 to red blood cells in
the PY01365 knockout parasite as compared to YM. While our
results identify PY01365 as a mediator of parasite virulence,
they also confirm that other members of Py235 are able to substitute for
PY01365
