The causative agent of Chagas disease, Trypanosoma cruzi, retains high genetic diversity, and its populations vary greatly in different geographic locations. T. cruzi mammalian hosts, including humans, also have high genetic variation, making it difficult to predict the disease outcome. Accordingly, this variability must be taken into account in studies aiming to determine the effect of polyparasitism on drug trials, vaccine studies, diagnosis or basic research. Therefore, there is a growing need to consider the interaction between the pathogen and the host immune system in mixed infections. In the present work, we show an in-depth analysis of gene expression in hearts from BALB/c mice infected with either Col1.7G2 or JG alone or a mixture of both strains. Col1.7G2 induced a higher Th1 inflammatory response, while JG produced a weaker activation of immune response genes. Furthermore, JGinfected mice showed a notable reduction in the expression of genes responsible for mitochondrial oxidative phosphorylation and protein synthesis. Interestingly, the mixture-infected group displayed changes in gene expression caused by both strains. Overall, we provided new insights into the host-pathogen interaction in the context of single and dual infection by showing the remarkable differences in the modulation of host gene expression by the two T. cruzi strains.

Perguntas e respostas para as 12 questões da "Taça das Casas". O tamanho da barra indica quantos participantes selecionaram a opção. A resposta correta é destacada em verde.

The protozoan Trypanosoma cruzi (T. cruzi) is a well-adapted parasite to mammalian hosts and 11 the pathogen of Chagas disease in humans. As both host and T. cruzi are highly genetically diverse, 12 many variables come into play during infection, making disease outcomes difficult to predict. One 13 important challenge in the field of Chagas disease research is determining the main factors leading 14 to parasite establishment in the chronic stage in some organs, mainly the heart and/or digestive 15 system. Our group previously showed that distinct strains of T. cruzi (JG and Col1.7G2) acquired 16 differential tissue distribution in the chronic stage in dually-infected BALB/c mice. To investigate 17 changes in the host triggered by the two distinct T. cruzi strains, we assessed the gene expression 18 profile of BALB/c mouse hearts infected with either JG, Col1.7G2 or an equivalent mixture of 19 both parasites during the initial phase of infection. This study demonstrates a clear distinction in 20 host gene expression modulation by both parasites. Col1.7G2 strongly activated Th1-polarized 21 immune signature genes, whereas JG showed only minor activation of the host immune response. 22 Moreover, JG strongly reduced the expression of genes for ribosomal proteins and mitochondrial 23 proteins related to the electron transport chain. Interestingly, evaluation of gene expression in mice 24 inoculated with the mixture of parasites showed expression profiles for both up-and down-25 regulated genes, indicating the coexistence of both parasite strains in the heart during the acute 26 phase. This study suggests that different strains of T. cruzi may be distinguished by their efficiency 27 in activating the immune system, modulating host energy and reactive oxygen species production 28 and decreasing protein synthesis during early infection, which may be crucial in defining parasite 29 persistence in specific organs. 31 Author Summary 32The causative agent of Chagas disease, Trypanosoma cruzi, retains high genetic diversity, and its 33 populations vary greatly across geographic locations. The T. cruzi mammalian hosts, including 34 humans, also have high genetic variation, making it difficult to predict the disease outcome. 35Accordingly, this variability must be taken into account in several studies aiming to interrogate 36 the effect of polyparasitism in drug trials, vaccines, diagnosis or basic research. Therefore, there 37 is a growing need to consider the interaction between the pathogen and the host immune system 38 in mixed infections. In the present work, we present an in-depth analysis of the gene expression of 39 hearts from BALB/c mice infected with Col1.7G2 and JG alone or a mixture of both strains. 40Col1.7G2 induced a higher Th1 inflammatory response, while JG exhibited a weaker activation of 41 immune response genes. Furthermore, JG-infected mice showed a notable reduction in the 42 expression of genes responsible for mitochondrial oxidative phosphorylation and protein 43 synthesis. Interestingly, the mixture...

Bioinformatics is a fast-evolving research field, requiring effective educational initiatives to bring computational knowledge to Life Sciences. Since 2017, an organizing committee composed of graduate students and postdoctoral researchers from the Universidade Federal de Minas Gerais (Brazil) promotes a week-long event named Summer Course in Bioinformatics (CVBioinfo). This event aims to diffuse bioinformatic principles, news, and methods mainly focused on audiences of undergraduate students. Furthermore, as the advent of the COVID-19 global pandemic has precluded in-person events, we offered the event in online mode, using free video transmission platforms. Herein, we present and discuss the insights obtained from promoting the Online Workshop in Bioinformatics (WOB) organized in November 2020, comparing it to our experience in previous in-person editions of the same event.

Splicing is a highly conserved, intricate mechanism intimately linked to transcription elongation, serving as a pivotal regulator of gene expression. Alternative splicing may generate specific transcripts incapable of undergoing translation into proteins, designated as unproductive. A plethora of respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), strategically manipulate the host’s splicing machinery to circumvent antiviral responses. During the infection, SARS-CoV-2 effectively suppresses interferon (IFN) expression, leading to B cell and CD8+ T cell leukopenia, while simultaneously increasing the presence of macrophages and neutrophils in patients with severe COVID-19. In this study, we integrated publicly available omics datasets to systematically analyze transcripts at the isoform level and delineate the nascent-peptide translatome landscapes of SARS-CoV-2-infected human cells. Our findings reveal a hitherto uncharacterized mechanism whereby SARS-CoV-2 infection induces the predominant expression of unproductive splicing isoforms in key IFN signaling genes, interferon-stimulated genes (ISGs), class I MHC genes, and splicing machinery genes, including IRF7, OAS3, HLA-B, and HNRNPH1. In stark contrast, cytokine and chemokine genes, such as IL6, CXCL8, and TNF, predominantly express productive (protein-coding) splicing isoforms in response to SARS-CoV-2 infection. We postulate that SARS-CoV-2 employs a previously unreported tactic of exploiting the host splicing machinery to bolster viral replication and subvert the immune response by selectively upregulating unproductive splicing isoforms from antigen presentation and antiviral response genes. Our study sheds new light on the molecular interplay between SARS-CoV-2 and the host immune system, offering a foundation for the development of novel therapeutic strategies to combat COVID-19.