TY - JOUR
T1 - Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice
AU - Mikolajczak, Sebastian A.
AU - Vaughan, Ashley M.
AU - Kangwanrangsan, Niwat
AU - Roobsoong, Wanlapa
AU - Fishbaugher, Matthew
AU - Yimamnuaychok, Narathatai
AU - Rezakhani, Nastaran
AU - Lakshmanan, Viswanathan
AU - Singh, Naresh
AU - Kaushansky, Alexis
AU - Camargo, Nelly
AU - Baldwin, Michael
AU - Lindner, Scott E.
AU - Adams, John H.
AU - Sattabongkot, Jetsumon
AU - Kappe, Stefan H.I.
N1 - Funding Information:
We would like to thank John Bial and Elizabeth Wilson (Yecuris Corporation) for assistance with the humanized mouse model, and members of the Prachumsri laboratory with help in mosquito rearing and sporozoite isolation. We would also like to thank Omar Vandal, Richard Elliot, and Brice Campo for helpful discussions concerning research presented in this manuscript. The research presented here was funded from Seattle Biomedical Research Institute internal financial support to S.H.I.K. in addition to a Global Health Grant from the Bill and Melinda Gates Foundation to S.H.I.K. (# OPP10215171 ), S.A.M. (# OPP1041422 ), J.H.A., and J.P. (# OPP1023643 ) and the Medicines for Malaria Venture (MMV) .
Publisher Copyright:
© 2015 Elsevier Inc.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2015/4/8
Y1 - 2015/4/8
N2 - Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites-hypnozoites. The lack of tractable P. vivax animal models constitutes an obstacle in examining P. vivax liver stage infection and drug efficacy. To overcome this obstacle, we have used human liver-chimeric (huHep) FRG KO mice as a model for P. vivax infection. FRG KO huHep mice support P. vivax sporozoite infection, liver stage development, and hypnozoite formation. We show complete P. vivax liver stage development, including maturation into infectious exo-erythrocytic merozoites as well as the formation and persistence of hypnozoites. Prophylaxis or treatment with the antimalarial primaquine can prevent and eliminate liver stage infection, respectively. Thus, P. vivax-infected FRG KO huHep mice are a model to investigate liver stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.
AB - Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites-hypnozoites. The lack of tractable P. vivax animal models constitutes an obstacle in examining P. vivax liver stage infection and drug efficacy. To overcome this obstacle, we have used human liver-chimeric (huHep) FRG KO mice as a model for P. vivax infection. FRG KO huHep mice support P. vivax sporozoite infection, liver stage development, and hypnozoite formation. We show complete P. vivax liver stage development, including maturation into infectious exo-erythrocytic merozoites as well as the formation and persistence of hypnozoites. Prophylaxis or treatment with the antimalarial primaquine can prevent and eliminate liver stage infection, respectively. Thus, P. vivax-infected FRG KO huHep mice are a model to investigate liver stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.
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U2 - 10.1016/j.chom.2015.02.011
DO - 10.1016/j.chom.2015.02.011
M3 - Article
C2 - 25800544
AN - SCOPUS:84927018652
VL - 17
SP - 526
EP - 535
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 4
ER -