Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum
| Autor: | Jürg Gysin, B. Pouvelle, Rosaura Hernández-Rivas, Emmanuel Bottius, Pierre Buffet, C. Benatar, Michael Lanzer, Artur Scherf |
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| Rok vydání: | 1998 |
| Předmět: |
Erythrocytes
Transcription Genetic Genes Protozoan Molecular Sequence Data Plasmodium falciparum CHO Cells Biology General Biochemistry Genetics and Molecular Biology Cell Line NAD+ Nucleosidase Antigens CD Cricetinae parasitic diseases Gene expression Cell Adhesion Antigenic variation Transcriptional regulation Animals Humans Gene family Gene silencing Amino Acid Sequence Endothelium RNA Messenger ADP-ribosyl Cyclase Saimiri Molecular Biology Gene Regulation of gene expression Genetics Pregnancy-associated malaria Membrane Glycoproteins General Immunology and Microbiology General Neuroscience Chondroitin Sulfates Brain Gene Expression Regulation Developmental Intercellular Adhesion Molecule-1 ADP-ribosyl Cyclase 1 Antigenic Variation Antigens Differentiation RNA Protozoan Research Article |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1093/emboj/17.18.5418 |
| Popis: | Members of the Plasmodium falciparum var gene family encode clonally variant adhesins, which play an important role in the pathogenicity of tropical malaria. Here we employ a selective panning protocol to generate isogenic P.falciparum populations with defined adhesive phenotypes for CD36, ICAM-1 and CSA, expressing single and distinct var gene variants. This technique has established the framework for examining var gene expression, its regulation and switching. It was found that var gene switching occurs in situ. Ubiquitous transcription of all var gene variants appears to occur in early ring stages. However, var gene expression is tightly regulated in trophozoites and is exerted through a silencing mechanism. Transcriptional control is mutually exclusive in parasites that express defined adhesive phenotypes. In situ var gene switching is apparently mediated at the level of transcriptional initiation, as demonstrated by nuclear run-on analyses. Our results suggest that an epigenetic mechanism(s) is involved in var gene regulation. |
| Databáze: | OpenAIRE |
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