Host kinase regulation of Plasmodium vivax dormant and replicating liver stages

Abstract

Upon transmission to the liver, Plasmodium vivax parasites form replicating schizonts, which progress to initiate blood-stage infection, or dormant hypnozoites that reactivate weeks to months after initial infection. P. vivax phenotypes in the field vary significantly, including the time to, and frequency of, relapse. Current evidence suggests that both parasite genetics and environmental factors underly this heterogeneity. Here, we applied an approach called kinase regression to evaluate the extent to which P. vivax liver-stage parasites are susceptible to changes in host kinase activity. We identified a role for a subset of host kinases in regulating the numbers of schizonts and hypnozoites, as well as schizont size, and characterized overlap as well as variability in host phosphosignaling dependencies between parasite forms across multiple patient isolates. Our data point to variability in host dependencies across P. vivax isolates, suggesting one possible origin of the heterogeneity observed in the field.