Leishmania histone H1 overexpression delays parasite cell-cycle progression, parasite differentiation and reduces Leishmania infectivity in vivo
Autor: | Maria Thiakaki, Sylvia Bisti, Georgia Konidou, Evangelia Xingi, Ketty Soteriadou, Despina Smirlis |
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Rok vydání: | 2006 |
Předmět: |
Transcriptional Activation
Cellular differentiation Protozoan Proteins Biology Microbiology Histones Mice Histone H1 Chlorocebus aethiops Animals Leishmania major Amastigote Molecular Biology Infectivity Mice Inbred BALB C Virulence Nocodazole Cell Cycle Kinetoplastida Cell Differentiation Cell cycle biology.organism_classification Virology In vitro Cell biology COS Cells NIH 3T3 Cells Leishmania donovani |
Zdroj: | Molecular microbiology. 60(6) |
ISSN: | 0950-382X |
Popis: | Episomal expression of Leishmania histone H1 sense mRNAs in Leishmania major promastigotes was found previously to result in overexpression of this molecule and to reduce parasite infectivity in vitro. Herein, we evaluated the in vivo infectivity of these transfectants, in BALB/c mice, and showed that it is dramatically reduced. No lesions were observed in this group of mice and this was associated with an extremely low number of parasites both in the footpad and in the draining lymph nodes. Interestingly, the transfectants-reduced infectivity was associated with a delay in their cell-cycle progression and differentiation to axenic amastigotes, assessed in vitro. Therefore, the dramatic reduction in their infectivity may be attributed to the above-mentioned phenotypic modifications. As the metazoan linker histone H1(0) homologue is known to delay cell-cycle progression in mammalian cells we investigated whether its Leishmania counterpart, which possesses homology to its C-terminal region, when expressed in mammalian cells may also affect their cell-cycle progression. It was thus shown that Leishmania histone H1 expressed in COS7 and NIH 3T3 cells, delays cell-cycle progression in these cells too. The latter strengthens the phenotype observed in Leishmania and provides evidence that critical functions of histone H1 molecules are conserved throughout evolution. |
Databáze: | OpenAIRE |
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