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Impact of Infection on Host Macrophage Nuclear Physiology and Nucleopore Complex Integrity

English version České info

Unicellular parasites of the genus Leishmania are the causative agent of leishmaniasis, a disease affecting 12 million people worldwide, mainly in tropical and subtropical regions of the developing world. They have evolved strategies to circumvent cellular defense mechanisms favouring their survival. This includes the cleavage and activation of proteins and the subsequent block of signals within the host cells. In this study we discovered that a Leishmania virulence factor, GP63, is able to reach host cell nuclei and affect protein transport from and into the nucleus. Through the analysis of the protein content of nuclei after parasite infection we revealed that Leishmania, predominantly through the protein cleaving enzyme GP63, can alter several processes within the nucleus, amongst others mechanisms associated with gene expression and nucleic acid metabolism. Thus, we here introduce a novel strategy of how Leishmania parasites may overcome host cell defense and ensure their own survival.

Vyšlo v časopise: Impact of Infection on Host Macrophage Nuclear Physiology and Nucleopore Complex Integrity. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004776
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004776

Souhrn

Unicellular parasites of the genus Leishmania are the causative agent of leishmaniasis, a disease affecting 12 million people worldwide, mainly in tropical and subtropical regions of the developing world. They have evolved strategies to circumvent cellular defense mechanisms favouring their survival. This includes the cleavage and activation of proteins and the subsequent block of signals within the host cells. In this study we discovered that a Leishmania virulence factor, GP63, is able to reach host cell nuclei and affect protein transport from and into the nucleus. Through the analysis of the protein content of nuclei after parasite infection we revealed that Leishmania, predominantly through the protein cleaving enzyme GP63, can alter several processes within the nucleus, amongst others mechanisms associated with gene expression and nucleic acid metabolism. Thus, we here introduce a novel strategy of how Leishmania parasites may overcome host cell defense and ensure their own survival.

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