Molecular Markers of Radiation Induced Attenuation in Intrahepatic Plasmodium falciparum Parasites
Publication Date
December 02, 2016
Authors
Miranda S. Oakley, Nitin Verma, Hong Zheng, Vivek Anantharaman, et al
Volume
11
Issue
12
Pages
e0166814
DOI
https://dx.plos.org/10.1371/journal.pone.0166814
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0166814
Scopus
85002342300
Mendeley
http://www.mendeley.com/research/molecular-markers-radiation-induced-attenuation-intrahepatic-plasmodium-falciparum-parasites
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Mendeley | Further Information

{"title"=>"Molecular markers of radiation induced attenuation in intrahepatic plasmodium falciparum parasites", "type"=>"journal", "authors"=>[{"first_name"=>"Miranda S.", "last_name"=>"Oakley", "scopus_author_id"=>"7005459490"}, {"first_name"=>"Nitin", "last_name"=>"Verma", "scopus_author_id"=>"57192248253"}, {"first_name"=>"Hong", "last_name"=>"Zheng", "scopus_author_id"=>"55207813600"}, {"first_name"=>"Vivek", "last_name"=>"Anantharaman", "scopus_author_id"=>"7005192673"}, {"first_name"=>"Kazuyo", "last_name"=>"Takeda", "scopus_author_id"=>"56661615500"}, {"first_name"=>"Yamei", "last_name"=>"Gao", "scopus_author_id"=>"55546303000"}, {"first_name"=>"Timothy G.", "last_name"=>"Myers", "scopus_author_id"=>"56686026500"}, {"first_name"=>"Phuong Thao", "last_name"=>"Pham", "scopus_author_id"=>"54970221100"}, {"first_name"=>"Babita", "last_name"=>"Mahajan", "scopus_author_id"=>"8658185500"}, {"first_name"=>"Nirbhay", "last_name"=>"Kumar", "scopus_author_id"=>"7401450245"}, {"first_name"=>"Davison", "last_name"=>"Sangweme", "scopus_author_id"=>"24176123200"}, {"first_name"=>"Abhai K.", "last_name"=>"Tripathi", "scopus_author_id"=>"7202810363"}, {"first_name"=>"Godfree", "last_name"=>"Mlambo", "scopus_author_id"=>"15077050800"}, {"first_name"=>"L.", "last_name"=>"Aravind", "scopus_author_id"=>"7006093805"}, {"first_name"=>"Sanjai", "last_name"=>"Kumar", "scopus_author_id"=>"56988058900"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0166814", "sgr"=>"85002342300", "pui"=>"613490910", "scopus"=>"2-s2.0-85002342300", "issn"=>"19326203", "pmid"=>"71691459", "isbn"=>"0002-9637"}, "id"=>"1cd9f19e-8a22-34bd-b980-8f8cce0cd593", "abstract"=>"Radiation attenuated sporozoite (RAS) vaccination has proved to be a promising approach for malaria vaccine development. While the host requirements for sterile immunity induced by RAS vaccination have been studied, the molecular events that render attenuation to sporozoites in response to radiation remain poorly understood. We performed genomewide transcriptional profiling of untreated verses radiation-treated intrahepatic parasites on days 3 and 6 post-invasion of human HepG2 hepatic cells by Plasmodium falciparum sporozoites of the 3D7 strain to identify parasite gene targets of growth attenuation and enhanced immune protection induced by radiation. Using this approach, we found that 180 parasite genes had significantly altered transcriptional expression in response to radiation on day 3 and 6 post-cultivation in hepatic cells. Among these novel biomarkers, we identified a signature of eight candidate parasite genes that associated with functionally diverse pathways that may regulate radiation induced cell cycle arrest of the parasite within the hepatocyte. In addition, a repertoire of 14 genes associated with protein translation is transcriptionally overexpressed within the parasite by radiation. We hypothesize that this radiation induced enhanced translational activity may be a contributing factor for the sterilizing immunity observed by RAS vaccination by increasing the pool of parasite antigens available for immune presentation either as processed epitopes on the hepatocyte surface or as released antigens from apoptotic infected hepatocytes . These results have significantly increased the repertoire of novel targets for 1) generating genetically attenuated parasite vaccine candidates 2) subunit vaccines against the hepatic stage cycle and 3) biomarkers of safety to define proper attenuation.", "link"=>"http://www.mendeley.com/research/molecular-markers-radiation-induced-attenuation-intrahepatic-plasmodium-falciparum-parasites", "reader_count"=>10, "reader_count_by_academic_status"=>{"Researcher"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>1, "Student > Doctoral Student"=>1}, "reader_count_by_user_role"=>{"Researcher"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>1, "Student > Doctoral Student"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>2}

Scopus | Further Information

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