Plasmodium falciparum PF10_0164 (ETRAMP10.3) Is an Essential Parasitophorous Vacuole and Exported Protein in Blood Stages

Upregulated in infectious sporozoites gene 4 (UIS4 ) encodes a parasitophorous vacuole membrane protein expressed in the sporozoite and liver stages of rodent malaria parasites. Parasites that lackUIS4 arrest in early liver-stage development, and vaccination of mice withuis4 − sporozoites confers sterile protection against challenge with infectious sporozoites. Currently, it remains unclear whether an ortholog ofUIS4 is carried in the human malaria parasitePlasmodium falciparum , although the genePF10_0164 has been identified as a candidate ortholog forUIS4 on the basis of synteny and structural similarity of the encoded protein. We show that PF10_0164 is expressed in sporozoites and blood stages ofP. falciparum , where it localizes to the parasitophorous vacuole, and is also exported to the host erythrocyte.PF10_0164 is refractory to disruption in asexual blood stages. Functional complementation was tested inPlasmodium yoelii by replacing the endogenous copy ofUIS4 withPF10_0164 . PF10_0164 localized to the parasitophorous vacuole membrane of liver stages, but transgenic parasites did not complete liver-stage development in mice. We conclude that PF10_0164 is a parasitophorous vacuole protein that is essential in asexual blood stages and that does not complementP. yoelii UIS4, and it is thus likely not a functional ortholog of UIS4.