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© 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) ; An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family and fundamental to both immune evasion and disease epidemiology within host populations. Recent studies have revealed that the VSG repertoire has a complex evolutionary history. Sequence diversity, genomic organization, and expression patterns are species-specific, which may explain other variations in parasite virulence and disease pathology. Evidence also shows that we may be underestimating the extent to what VSGs are repurposed beyond their roles as variant antigens, establishing a need to examine VSG functionality more deeply. Here, we review sequence variation within the VSG gene family, and highlight the many opportunities to explore their likely diverse contributions to parasite survival. ; S.S.P. is funded by the European Union's Horizon 2020 research and innovation program through a Marie Skłodowska-Curie Individual Standard European Fellowship , under grant agreement no. 839960 . A.P.J. is funded by a Leverhulme Trust Research Fellowship ( RF-2020-413 ). L.M.F. is an Investigator CEEC of the Fundação para a Ciência e a Tecnologia ( CEECIND/03322/2018 ) and the laboratory is funded by the ERC (FatTryp, ref. 771714 ). ; info:eu-repo/semantics/publishedVersion

© 2019 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ; Intravital microscopy allows the visualisation of how pathogens interact with host cells and tissues in living animals in real time. This method has enabled key advances in our understanding of host-parasite interactions under physiological conditions. A combination of genetics, microscopy techniques, and image analysis have recently facilitated the understanding of biological phenomena in living animals at cellular and subcellular resolution. In this review, we summarise findings achieved by intravital microscopy of the skin and adipose tissues upon infection with various parasites, and we present a view into possible future applications of this method. ; M. D. N. was funded by Long Term EMBO Postdoctoral fellowship ALTF 1048-2016. G. R. M. was funded by Wellcome Trust Grant 095507. L. M. F. was funded by FCT (IF/01050/2014) and ERC (FatTryp, ref. 771714). Part of this work was funded by a French Government Investissement d'Avenir programme, Laboratoire d'Excellence "Integrative Biology of Emerging Infectious Diseases" (ANR-10-LABX-62-IBEID) and by the French National Agency for Scientific Research (Young Researcher Grant ANR-14-CE14-0019-01). B.R. was funded by the Institut Pasteur. F.F. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Projektnumber 240245660 - SFB 1129. ; info:eu-repo/semantics/publishedVersion

Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC) ; The parasite Trypanosoma brucei causes African sleeping sickness that is fatal to patients if untreated. Parasite differentiation from a replicative slender form into a quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation in other eukaryotes. To determine whether lncRNAs are also involved in parasite differentiation, we used RNA sequencing to survey the T. brucei genome, identifying 1428 previously uncharacterized lncRNA genes. We find that grumpy lncRNA is a key regulator that promotes parasite differentiation into the quiescent stumpy form. This function is promoted by a small nucleolar RNA encoded within the grumpy lncRNA. snoGRUMPY binds to messenger RNAs of at least two stumpy regulatory genes, promoting their expression. grumpy overexpression reduces parasitemia in infected mice. Our analyses suggest that T. brucei lncRNAs modulate parasite-host interactions and provide a mechanism by which grumpy regulates cell differentiation in trypanosomes. ; This work was supported in part by Fundação para a Ciência e Tecnologia (FCT) grant, awarded to F.G. and entitled "Long noncoding RNAs as new diagnostic biomarkers for African Sleeping sickness" (PTDC/DTPEPI/7099/2014, start date: 1 January 2016, end date: 31 December 2018); also by Howard Hughes Medical Institute International Early Career Scientist Program (project title: "How parasites use epigenetics to evade host defenses," project no. 55007419, start date: 1 February 2012, end date: 31 January 2017); and by the European Research Council (project title: "Exploring the hidden life of African trypanosomes: parasite fat tropism and implications for the disease," project no. 771714, start date: 1 August 2018, end date: 31 ...

Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies. ; This work was supported by a grant from the Bill & Melinda Gates Foundation ( OPP1150674 ). KSR gratefully acknowledges funding of the NTD Modelling Consortium by the Bill & Melinda Gates Foundation in partnership with the Task Force for Global Health under grant number OPP1053230 . AML, BB, EM, GS, HI, MK, VJ, and VL are supported by TrypanoGen funded by the Wellcome Trust (grant number 099310/Z/12/Z ). NC acknowledges funding from the Bill & Melinda Gates Foundation under grant OPP1156227 . LMF is funded by Fundacao para a Ciencia e Tecnologia ( IF/01050/2014 ). FAO contribution to this study was provided in the framework of the Programme against African Trypanosomosis (PAAT), and supported by the Government of Italy (FAO Project 'Improving food security in sub-Saharan Africa by supporting the progressive reduction of tsetse-transmitted trypanosomosis in the framework of the NEPAD', codes GTFS/RAF/474/ITA and GCP/RAF/502/ITA). The funders had no role in design, decision to publish, or preparation of the manuscript. The views, opinions, assumptions or any other information set out in this article are solely those of the authors. ; Sí