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Title: | Plasmodium vivax spleen-dependent genes encode antigens associated with cytoadhesion and clinical protection. |
Author: | Fernández Becerra, Carmen Bernabeu Aznar, Maria Castellanos, Angélica Correa, Bruna Obadia, Thomas Ramírez, Miriam Rui, Edmilson Hentzschel, Franziska López Montañés, Maria Ayllon Hermida, Alberto Martín Jaular, Lorena Elizalde Torrent, Aleix Siba, Peter Vêncio, Ricardo Z. Arévalo Herrera, Myriam Herrera, Sócrates Alonso, Pedro Mueller, Ivo Portillo, Hernando A. del |
Keywords: | Malària Papua Nova Guinea Malaria Papua New Guinea |
Issue Date: | 2020 |
Publisher: | National Academy of Sciences |
Abstract: | The most widely distributed human malaria parasite, causes severe clinical syndromes despite low peripheral blood parasitemia. This conundrum is further complicated as cytoadherence in the microvasculature is still a matter of investigations. Previous reports in " - ", another parasite species shown to infect humans, demonstrated that variant genes involved in cytoadherence were dependent on the spleen for their expression. Hence, using a global transcriptional analysis of parasites obtained from spleen-intact and splenectomized monkeys, we identified 67 " - " genes whose expression was spleen dependent. To determine their role in cytoadherence, two " - " transgenic lines expressing two variant proteins pertaining to VIR and Pv-FAM-D multigene families were used. Cytoadherence assays demonstrated specific binding to human spleen but not lung fibroblasts of the transgenic line expressing the VIR14 protein. To gain more insights, we expressed five " - " spleen-dependent genes as recombinant proteins, including members of three different multigene families (VIR, Pv-FAM-A, Pv-FAM-D), one membrane transporter (SECY), and one hypothetical protein (HYP1), and determined their immunogenicity and association with clinical protection in a prospective study of 383 children in Papua New Guinea. Results demonstrated that spleen-dependent antigens are immunogenic in natural infections and that antibodies to HYP1 are associated with clinical protection. These results suggest that the spleen plays a major role in expression of parasite proteins involved in cytoadherence and can reveal antigens associated with clinical protection, thus prompting a paradigm shift in " - " biology toward deeper studies of the spleen during infections |
Note: | Reproducció del document publicat a: http://dx.doi.org/ 10.1073/pnas.1920596117 |
It is part of: | Proceedings of the National Academy of Sciences of the United States of America, 2020, vol 117, num 23 |
URI: | http://hdl.handle.net/2445/182978 |
Related resource: | http://dx.doi.org/ 10.1073/pnas.1920596117 |
ISSN: | 0027-8424 |
Appears in Collections: | Articles publicats en revistes (ISGlobal) |
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Fernandez_C_Proc_Natl_Acad_Sci_USA_2020.pdf | 1.59 MB | Adobe PDF | View/Open |
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