Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice

Sebastian A. Mikolajczak; Ashley M. Vaughan; Niwat Kangwanrangsan; Wanlapa Roobsoong; Matthew Fishbaugher; Narathatai Yimamnuaychok; Nastaran Rezakhani; Viswanathan Lakshmanan; Naresh Singh; Alexis Kaushansky; Nelly Camargo; Michael Baldwin; Scott E. Lindner; John H. Adams; Jetsumon Sattabongkot; Stefan H.I. Kappe

doi:10.1016/j.chom.2015.02.011

Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice

Sebastian A. Mikolajczak, Ashley M. Vaughan, Niwat Kangwanrangsan, Wanlapa Roobsoong, Matthew Fishbaugher, Narathatai Yimamnuaychok, Nastaran Rezakhani, Viswanathan Lakshmanan, Naresh Singh, Alexis Kaushansky, Nelly Camargo, Michael Baldwin, Scott E. Lindner, John H. Adams, Jetsumon Sattabongkot, Stefan H.I. Kappe

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article

90 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	526-535
Number of pages	10
Journal	Cell Host and Microbe
Volume	17
Issue number	4
DOIs	https://doi.org/10.1016/j.chom.2015.02.011
State	Published - Apr 8 2015

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All Science Journal Classification (ASJC) codes

Parasitology
Microbiology
Virology

Cite this

Mikolajczak, S. A., Vaughan, A. M., Kangwanrangsan, N., Roobsoong, W., Fishbaugher, M., Yimamnuaychok, N., Rezakhani, N., Lakshmanan, V., Singh, N., Kaushansky, A., Camargo, N., Baldwin, M., Lindner, S. E., Adams, J. H., Sattabongkot, J., & Kappe, S. H. I. (2015). Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice. Cell Host and Microbe, 17(4), 526-535. https://doi.org/10.1016/j.chom.2015.02.011

Mikolajczak, Sebastian A. ; Vaughan, Ashley M. ; Kangwanrangsan, Niwat ; Roobsoong, Wanlapa ; Fishbaugher, Matthew ; Yimamnuaychok, Narathatai ; Rezakhani, Nastaran ; Lakshmanan, Viswanathan ; Singh, Naresh ; Kaushansky, Alexis ; Camargo, Nelly ; Baldwin, Michael ; Lindner, Scott E. ; Adams, John H. ; Sattabongkot, Jetsumon ; Kappe, Stefan H.I. / Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice. In: Cell Host and Microbe. 2015 ; Vol. 17, No. 4. pp. 526-535.

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title = "Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice",

abstract = "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.",

author = "Mikolajczak, {Sebastian A.} and Vaughan, {Ashley M.} and Niwat Kangwanrangsan and Wanlapa Roobsoong and Matthew Fishbaugher and Narathatai Yimamnuaychok and Nastaran Rezakhani and Viswanathan Lakshmanan and Naresh Singh and Alexis Kaushansky and Nelly Camargo and Michael Baldwin and Lindner, {Scott E.} and Adams, {John H.} and Jetsumon Sattabongkot and Kappe, {Stefan H.I.}",

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Mikolajczak, SA, Vaughan, AM, Kangwanrangsan, N, Roobsoong, W, Fishbaugher, M, Yimamnuaychok, N, Rezakhani, N, Lakshmanan, V, Singh, N, Kaushansky, A, Camargo, N, Baldwin, M, Lindner, SE, Adams, JH, Sattabongkot, J & Kappe, SHI 2015, 'Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice', Cell Host and Microbe, vol. 17, no. 4, pp. 526-535. https://doi.org/10.1016/j.chom.2015.02.011

Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice. / Mikolajczak, Sebastian A.; Vaughan, Ashley M.; Kangwanrangsan, Niwat; Roobsoong, Wanlapa; Fishbaugher, Matthew; Yimamnuaychok, Narathatai; Rezakhani, Nastaran; Lakshmanan, Viswanathan; Singh, Naresh; Kaushansky, Alexis; Camargo, Nelly; Baldwin, Michael; Lindner, Scott E.; Adams, John H.; Sattabongkot, Jetsumon; Kappe, Stefan H.I.

In: Cell Host and Microbe, Vol. 17, No. 4, 08.04.2015, p. 526-535.

Research output: Contribution to journal › Article

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.

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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10.1016/j.chom.2015.02.011