Genovesio, AGiardini, MAKwon, Y-Jde Macedo Dossin, FCho, SYKim, NYKim, HCJung, SYSchenkman, SAlmeida, ICEmans, NFreitas-Junior, LH2011-06-102011-06-102011-05Genovesio, 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.00197331932-6203http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0019733http://hdl.handle.net/10204/5056Copyright: 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.0019733The 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.enChagas diseaseTrypanosoma cruziT. cruzi infectionTropical infectionDrug developmentRNAi screeningArticleGenovesio, A., Giardini, M., Kwon, Y., de Macedo Dossin, F., Cho, S., Kim, N., ... Freitas-Junior, L. (2011). Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection. http://hdl.handle.net/10204/5056Genovesio, A, MA Giardini, Y-J Kwon, F de Macedo Dossin, SY Cho, NY Kim, HC Kim, et al "Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection." (2011) http://hdl.handle.net/10204/5056Genovesio A, Giardini M, Kwon Y, de Macedo Dossin F, Cho S, Kim N, et al. Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection. 2011; http://hdl.handle.net/10204/5056.TY - Article AU - Genovesio, A AU - Giardini, MA AU - Kwon, Y-J AU - de Macedo Dossin, F AU - Cho, SY AU - Kim, NY AU - Kim, HC AU - Jung, SY AU - Schenkman, S AU - Almeida, IC AU - Emans, N AU - Freitas-Junior, LH AB - 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. DA - 2011-05 DB - ResearchSpace DP - CSIR KW - Chagas disease KW - Trypanosoma cruzi KW - T. cruzi infection KW - Tropical infection KW - Drug development KW - RNAi screening LK - https://researchspace.csir.co.za PY - 2011 SM - 1932-6203 T1 - Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection TI - Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection UR - http://hdl.handle.net/10204/5056 ER -