In vivo transcriptome of Plasmodium falciparum reveals overexpression of transcripts that encode surface proteins.
Infections with the human parasite Plasmodium falciparum continue to present a great challenge to global health. Fundamental questions regarding the molecular basis of virulence and immune evasion in P. falciparum have been only partially answered. Because of the parasite's intracellular location and complex life cycle, standard genetic approaches to the study of the pathogenesis of malaria have been limited. The present study presents a novel approach to the identification of the biological processes involved in host-pathogen interactions, one that is based on the analysis of in vivo P. falciparum transcripts. We demonstrate that a sufficient quantity of P. falciparum RNA transcripts can be derived from a small blood sample from infected patients for whole-genome microarray analysis. Overall, excellent correlation was observed between the transcriptomes derived from in vivo samples and in vitro samples with ring-stage P. falciparum 3D7 reference strain. However, gene families that encode surface proteins are overexpressed in vivo. Moreover, this analysis has identified a new family of hypothetical genes that may encode surface variant antigens. Comparative studies of the transcriptomes derived from in vivo samples and in vitro 3D7 samples may identify important strategies used by the pathogen for survival in the human host and highlight, for vaccine development, new candidate antigens that were not previously identified through the use of in vitro cultures.
Daily
Johanna P
JP
Department of Immunology and Infectious Disease, Harvard School of Public Health, Boston, Massachusetts 02115, USA. jdaily@partners.org
Le Roch
Karine G
KG
Sarr
Ousmane
O
Ndiaye
Daouda
D
Lukens
Amanda
A
Zhou
Yingyao
Y
Ndir
Omar
O
Mboup
Soulyemane
S
Sultan
Ali
A
Winzeler
Elizabeth A
EA
Wirth
Dyann F
DF
D000222:Adaptation, Physiological; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016053:RNA, Protozoan / Q000032:analysis / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D008565:Membrane Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan