STK35L1 regulates Plasmodium infection and expression of cell cycle genes during liver stage of malaria

Abstract Protein kinases of both the parasite and host are crucial in parasite invasion and survival and might be drug targets against drug-resistant malaria. STK35L1 was among the top five hits in kinome-wide screening, suggesting a role in malaria’s liver stage. The function of STK35L1 in malaria is not known yet. We found that STK35L1 was highly upregulated during the infection of P. berghei in HepG2 cells and mice liver. Knockdown of STK35L1 remarkably suppressed the sporozoite infection in hepatocytes. STAT3 is upregulated and phosphorylated during P. berghei sporozoites infection. We found that STAT3 activation is required for both STK35L1 and STAT3 upregulation. Furthermore, ten cell cycle genes were upregulated in the sporozoite-infected hepatocytes. Knockdown of STK35L1 completely inhibited the upregulation of these genes. We identified STK35L1 as a host kinase that plays an obligatory role in malaria’s liver stage. It may be a potential drug target against drug-resistant malaria.