title: Experimental cerebral malaria is suppressed by disruption of nucleoside transporter 1 but not purine nucleoside phosphorylase.
abstract: Protozoan parasites rely on purine nucleosides supplied by the host because they are unable to synthesise purine rings denovo. Nucleoside transporter 1 (NT1) and purine nucleoside phosphorylase (PNP) play an essential role in purine salvage in Plasmodium. It is unclear whether severe pathology, such as cerebral malaria (CM), develops in hosts infected with Plasmodium parasites that lack activity of NT1 or PNP. Plasmodium berghei (Pb) ANKA-infected mice show features similar to human CM, such as cerebral paralysis and cerebral haemorrhage. Therefore, Pb ANKA infection in mice is a good experimental model of CM. In this study, we generated pbnt1-disrupted Pb ANKA (Δpbnt1 parasites) and pbpnp-disrupted Pb ANKA (Δpbpnp parasites), and investigated the effect of pbnt1 or pbpnp disruption on the outcome of infection with Pb ANKA. We showed that the rapid increase of wild-type Pb ANKA (WT parasites) in mice early in infection was significantly inhibited by disruption of pbnt1. Moreover, Δpbnt1 parasite-infected mice showed neither cerebral paralysis nor cerebral haemorrhage, and all mice spontaneously recovered from infection. By contrast, mice infected with Δpbpnp parasites showed features similar to those of mice infected with WT parasites. In this study, we demonstrated that the high virulence of Pb ANKA in the asexual phase is suppressed by disruption of pbnt1 but not pbpnp.
authors: Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan.
authors: Mamoru
authors: M
authors: Niikura
authors: Shin-Ichi
authors: S
authors: Inoue
authors: Shoichirou
authors: S
authors: Mineo
authors: Yutaroh
authors: Y
authors: Yamada
authors: Izumi
authors: I
authors: Kaneko
authors: Shiroh
authors: S
authors: Iwanaga
authors: Masao
authors: M
authors: Yuda
authors: Fumie
authors: F
authors: Kobayashi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000469:parasitology; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006801:Humans; D016779:Malaria, Cerebral / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D033703:Nucleoside Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D033703:Nucleoside Transport Proteins; D015800:Protozoan Proteins; D011683:Purine-Nucleoside Phosphorylase