Changes in the Expression of Human Cell Division Autoantigen-1 Influence Toxoplasma gondii Growth and Development

• DOI: 10.1371/journal.ppat.0020105
• Publication Date: 2006-10-20T18:35:02Z
• Authors: Jay R Radke; Robert G Donald; Amy Eibs; Maria E Jerome; Michael S Behnke; Paul Liberator; Michael W White
• Keywords: Male; Transcription, Genetic; QH301-705.5; Protozoan Proteins; Autoantigens; Host-Parasite Interactions; 03 medical and health sciences; Animals; Humans; Pyrroles; RNA, Messenger; Biology (General); RNA, Small Interfering; Cells, Cultured; Heat-Shock Proteins; Oligonucleotide Array Sequence Analysis; 0303 health sciences; DNA; RC581-607; DNA, Protozoan; Fibroblasts; 3. Good health; Phenotype; Gene Expression Regulation; Multivariate Analysis; Immunologic diseases. Allergy; Toxoplasma; Research Article

Toxoplasma is a significant opportunistic pathogen in AIDS, and bradyzoite differentiation the critical step pathogenesis of chronic infection. Bradyzoite development has an apparent tropism for cells tissues central nervous system, suggesting need specific molecular environment host cell, but it unknown whether this parasite directed or result features to cell itself. We have determined that trisubstituted pyrrole acts directly on human murine slow tachyzoite replication induce bradyzoite-specific gene expression type II III strain parasites not I strains. New mRNA synthesis was required indicates novel transcripts encode signals were able development. applied multivariate microarray analyses identify correlate with phenotypes. Human division autoantigen-1 (CDA1) identified analysis, small interfering RNA knockdown demonstrated CDA1 causes inhibition leads subsequently induction differentiation. Overexpression alone growth proteins, thus these results demonstrate changes transcription can influence enable Investigation biochemical pathways respect variation response will help provide understanding link(s) between