A Plasmodium vivax genetic cross to investigate molecular determinants of chloroquine response

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NIAID	INFECTDIS-5

Authors

• JM Sa
• SR Kaslow
• J Mu
• E Kessler
• RE Salzman
• V Melendez-Muniz
• MJ Lope-Barragan
• S Velmurugan
• YF Abebe
• ER James
• A Richman
• S Chakravarty
• BKL Sim
• SL Hoffman
• RW Gwadz
• TE Wellems

Abstract

To investigate determinants of Plasmodium vivax chloroquine (CQ) resistance we have generated a genetic cross between two parasite lines with distinct CQ responses. A chimpanzee was infected with a mixture of these parental lines to produce infectious gametocytes for cross-fertilization in Anopheles mosquitoes. Recombinant sporozoites from the infected mosquitoes were purified and cryopreserved and subsequently used to re-inoculate the same chimpanzee after it was completely cured of the parental lines infection. When parasitemia was detected in the re-inoculated chimpanzee, pools of mixed intraerythrocytic recombinant progeny were collected and inoculated into Aotus monkeys. Progeny in these pools showed responses spanning the range of the parental lines, including some parasites surviving a total CQ dose of 15 mg/kg (5 mg/kg/day x 3 days). Comparison of genetic markers in the mixed progeny before and after CQ treatment identifies regions of chromosomes that may be subject to linkage group selection and contain possible candidate genes. The P. vivax ortholog of the P. falciparum CQ resistance transporter gene (pfcrt ortholog, pvcrt-o) resides in one of these chromosome regions.

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