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Show simple item record Genovesio, A Giardini, MA Kwon, Y-J de Macedo Dossin, F Cho, SY Kim, NY Kim, HC Jung, SY Schenkman, S Almeida, IC Emans, N Freitas-Junior, LH 2011-06-10T07:32:19Z 2011-06-10T07:32:19Z 2011-05
dc.identifier.citation Genovesio, A, Giardini, MA, Kwon, Y-J et al. 2011. Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection. PLoS ONE, vol. 6(5), e19733. doi:10.1371/journal.pone.0019733 en_US
dc.identifier.issn 1932-6203
dc.description Copyright: 2011 Genovesio et al. This is the definitive version of the work. This version is published in PLoS ONE 6(5): e19733. doi:10.1371/journal.pone.0019733 en_US
dc.description.abstract The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, the authors performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, they recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy. en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.relation.ispartofseries Workflow;6646
dc.subject Chagas disease en_US
dc.subject Trypanosoma cruzi en_US
dc.subject T. cruzi infection en_US
dc.subject Tropical infection en_US
dc.subject Drug development en_US
dc.subject RNAi screening en_US
dc.title Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection en_US
dc.type Article en_US

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