@article{72bf483fbead4e0ca37f9ce54b39aa39,
title = "Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross",
abstract = "Mainstay treatment for Plasmodium vivax malaria has long relied on chloroquine (CQ) against blood-stage parasites plus primaquine against dormant liver-stage forms (hypnozoites), however drug resistance confronts this regimen and threatens malaria control programs. Understanding the basis of P. vivax chloroquine resistance (CQR) will inform drug discovery and malaria control. Here we investigate the genetics of P. vivax CQR by a cross of parasites differing in drug response. Gametocytogenesis, mosquito infection, and progeny production are performed with mixed parasite populations in nonhuman primates, as methods for P. vivax cloning and in vitro cultivation remain unavailable. Linkage mapping of progeny surviving >15 mg/kg CQ identifies a 76 kb region in chromosome 1 including pvcrt, an ortholog of the Plasmodium falciparum CQR transporter gene. Transcriptional analysis supports upregulated pvcrt expression as a mechanism of CQR.",
author = "S{\'a}, {Juliana M.} and Kaslow, {Sarah R.} and {Moraes Barros}, {Roberto R.} and Brazeau, {Nicholas F.} and Parobek, {Christian M.} and Dingyin Tao and Salzman, {Rebecca E.} and Gibson, {Tyler J.} and Soundarapandian Velmurugan and Krause, {Michael A.} and Viviana Melendez-Muniz and Kite, {Whitney A.} and Han, {Paul K.} and Eastman, {Richard T.} and Adam Kim and Kessler, {Evan G.} and Yonas Abebe and James, {Eric R.} and Sumana Chakravarty and Sachy Orr-Gonzalez and Lambert, {Lynn E.} and Theresa Engels and Thomas, {Marvin L.} and Fasinu, {Pius S.} and David Serre and Gwadz, {Robert W.} and Larry Walker and DeConti, {Derrick K.} and Jianbing Mu and Bailey, {Jeffrey A.} and Sim, {B. Kim Lee} and Hoffman, {Stephen L.} and Fay, {Michael P.} and Dinglasan, {Rhoel R.} and Juliano, {Jonathan J.} and Wellems, {Thomas E.}",
note = "Funding Information: We thank Ahlin Bruce, Billeta Lewis, Faith Sentz, Sekou Savane, Andy Limeric, Kevin Ham, John Bacher, Randy Elkins, Anthony Cook, Sali Muhammad, Zac Pippin, Bharathi Avula, Andre Laughinghouse, and Kevin Lee for their efforts in support of this project. This study was supported by the Intramural Research Program of the National Institute Funding Information: of Allergy and Infectious Diseases, National Institutes of Health; also funded in part by an 1R21AI111108 award to J.J.J., a seed grant from the Bloomberg Family Foundation to R.R.D., and T32 grants GM008719 and GM007092 to C.M.P. Publisher Copyright: {\textcopyright} 2019, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-12256-9",
language = "English (US)",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}