Molecular Markers of Radiation Induced Attenuation in Intrahepatic Plasmodium falciparum Parasites

Autor: Sanjai Kumar, L. Aravind, Nitin Verma, Abhai K. Tripathi, Kazuyo Takeda, Miranda S. Oakley, Davison Sangweme, Vivek Anantharaman, Yamei Gao, Hong Zheng, Nirbhay Kumar, Babita Mahajan, Godfree Mlambo, Timothy G. Myers, Phuong Thao Pham
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Plasmodium
Cell
Cell Membranes
Protozoan Proteins
lcsh:Medicine
Biochemistry
Transmembrane Transport Proteins
Animal Cells
Gene expression
Medicine and Health Sciences
Malaria
Falciparum
lcsh:Science
Protozoans
Multidisciplinary
biology
Malaria vaccine
Liver cell
Malarial Parasites
Cell cycle
Cell biology
medicine.anatomical_structure
Liver
Sporozoites
Female
Cellular Types
Anatomy
Cellular Structures and Organelles
Research Article
Plasmodium falciparum
Vaccines
Attenuated
Cell Line
03 medical and health sciences
Anopheles
Malaria Vaccines
DNA-binding proteins
Parasite Groups
medicine
Parasitic Diseases
Animals
Humans
Inner membrane complex
Biology and life sciences
lcsh:R
Organisms
Proteins
Membrane Proteins
Cell Biology
biology.organism_classification
Parasitic Protozoans
030104 developmental biology
Membrane protein
Gene Expression Regulation
Gamma Rays
Hepatocytes
Parasitology
lcsh:Q
Apicomplexa
Biomarkers
Zdroj: PLoS ONE, Vol 11, Iss 12, p e0166814 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: Experimental immunization with radiation attenuated sporozoites (RAS) and genetically attenuated sporozoites has proved to be a promising approach for malaria vaccine development. However, parasite biomarkers of growth attenuation and enhanced immune protection in response to radiation remain poorly understood. Here, we report on the effect of an attenuating dose of γ-irradiation (15 krad) on the Plasmodium falciparum sporozoite (PfSPZ) ultrastructure by electron microscopy, growth rate of liver stage P. falciparum in liver cell cultures, and genome-wide transcriptional profile of liver stage parasites by microarray. We find that γ-irradiation treated PfSPZ retained a normal cellular structure except that they were vacuous with a partially disrupted plasma membrane and inner membrane complex. A similar infection rate was observed by γ-irradiation-treated and untreated PfSPZ in human HCO-4 liver cells (0.47% versus 0.49%, respectively) on day 3 post-infection. In the microarray studies, cumulatively, 180 liver stage parasite genes were significantly transcriptionally altered on day 3 and/or 6 post-infection. Among the transcriptionally altered biomarkers, we identified a signature of seven candidate parasite genes that associated with functionally diverse pathways that may regulate radiation induced cell cycle arrest of the parasite within the hepatocyte. A repertoire of 14 genes associated with protein translation is transcriptionally overexpressed within the parasite by radiation. Additionally, 37 genes encode proteins expressed on the cell surface or exported into the host cell, 4 encode membrane associated transporters, and 10 encode proteins related to misfolding and stress-related protein processing. These results have significantly increased the repertoire of novel targets for 1) biomarkers of safety to define proper attenuation, 2) generating genetically attenuated parasite vaccine candidates, and 3) subunit candidate vaccines against liver stage malaria.
Databáze: OpenAIRE
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