Biology subjects

Ribeiro-Alves, M.

Publications and source records attributed to Ribeiro-Alves, M..

10 recordsLinked to original sources

bioRxiv2023

HIHISIV: a database of gene expression in HIV and SIV host immune response

In the battle of the host against lentiviral pathogenesis, the immune response is crucial. However, several questions remain unanswered about the interaction with different viruses and their influence on disease progression. The simian immunodeficiency virus (SIV) infecting nonhuman primates (NHP) is widely used as a model for the study of the human immunodeficiency virus (HIV). Both because they are evolutionarily linked and because they share physiological and anatomical similarities that are largely explored to understand the disease progression. The HIHISIV database was developed to support researchers to integrate and evaluate the large number of transcriptional data associated with the presence/absence of the pathogen (SIV or HIV) and the host response (NHP and human). The datasets are composed of microarray and RNA-Seq gene expression data that were selected, curated, analyzed, enriched, and stored in a relational database. Six query templates comprise the main data analysis functions and the resulting information can be downloaded. The HIHISIV database provides accurate resources for browsing and visualizing results and for more robust analyses of pre-existing data in transcriptome repositories. Database URLhttps://hihisiv.github.io

bioinformatics↗

bioRxiv2023

Transcriptional profile of ribosome-associated quality control components and their associated phenotypes in mammalian cells

During protein synthesis, organisms detect translation defects that induce ribosome stalling and result in protein aggregation. The Ribosome-associated Quality Control (RQC) complex, comprising TCF25, LTN1, and NEMF, is responsible for identifying incomplete protein products from unproductive translation events, targeting them for degradation. Though RQC disruption causes adverse effects on vertebrate neurons, data regarding mRNA/protein expression and regulation across tissues are lacking. Employing high-throughput methods, we analyzed public datasets to explore RQC gene expression and phenotypes. Our findings revealed a widespread expression of RQC components in human tissues; however, silencing of RQC yielded only mild negative effects on cell growth. Notably, TCF25 exhibited elevated mRNA levels that were not reflected in protein content. We experimentally demonstrated that this disparity arises from post-translational protein degradation by the proteasome. Additionally, we observed that cellular aging marginally influences RQC expression, leading to reduced mRNA levels in specific tissues. Our results suggest the necessity of RQC expression in all mammalian tissues. Nevertheless, when RQC falters, alternative mechanisms seem to compensate, ensuring cell survival under non-stress conditions.

bioinformatics↗

bioRxiv2020

Natural variation of the cardiac transcriptome in humans

We investigated the gene-expression variation among humans by analyzing previously published mRNA-seq and ribosome footprint profiling (RP) of heart left-ventricles from healthy donors. We ranked the genes according to their coefficient of variation values and found that the top 5% most variable genes had special features compared to the rest of the genome, such as lower mRNA levels and shorter half-lives coupled to increased translation efficiency. We observed that these genes are mostly involved with immune response and have a pleiotropic effect on disease phenotypes, indicating that asymptomatic conditions contribute to the gene expression diversity of healthy individuals.

genomics↗

bioRxiv2020

Influence of Activating and Inhibitory Killer Immunoglobulin-Like Receptors (KIR) genes on the recurrence rate of ocular toxoplasmosis in Brazil

BackgroundRecurrence is a hallmark of ocular toxoplasmosis (OT), and conditions that influence its occurrence remain a challenge. Natural killer cells (NK) are effectors cells whose primary function is the cytotoxic activity against many parasites, including Toxoplasma gondii. Among the NK cell receptors, immunoglobulin-like receptors (KIR) deserve attention due to their high polymorphism. This study aimed to analyze the influence of KIR gene polymorphism in the course of OT infection and its association with recurrences after an active episode. MethodsNinety-six patients from the Ophthalmologic Clinic of the National Institute of Infectology Evandro Chagas (INI/Fiocruz/RJ, Brazil) were followed for up to five years. After DNA extraction, genotyping of the patients was performed by PCR-SSO utilizing Luminex equipment for reading. During follow-up, 57.4% had a recurrence. ResultsWe identified 25 KIR genotypes and found a higher frequency of genotypes 1 (31.7%) with worldwide distribution. We note that the KIR2DL2 inhibitor gene and the gene activator KIR2DS2 were more frequent in patients without recurrence (P = 0.03 and P = 0.02, respectively). Additionally, we observed one activating gene, KIR2DS1, associated with more than four times faster progression to the development of recurrent ocular toxoplasmosis than individuals without this gene (aRR = 4.6, P = 0.04). ConclusionThe KIR2DL2 and KIR2DS2 are associated as possible protection markers and the KIR2DS1 acting as a possible susceptibility marker. Additionally, the lower proportion of activating genes observed in individuals with recurrence corroborating with the hypothesis that these individuals are more susceptible to ocular toxoplasmosis recurrence (OTR).

molecular biology↗

bioRxiv2019

Congenital Zika Syndrome is associated with maternal genetic background

BackgroundHost factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. MethodsWe accessed samples from Zika pregnancies, conducted a case-control study to verify whether interferon alfa receptor 1 (IFNAR1) and interferon lambda 2 and 4 (IFNL2/4) single nucleotide polymorphisms (SNPs) contribute to CZS newborn outcome and we characterized placenta gene expression profile at term. FindingsNewborns carrying CG/CC genotypes of rs2257167 in IFNAR1 presented higher risk of developing CZS (OR=3.73; IC=1.36-10.21; Pcorrected=0.02646). No association between IFNL SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of IFNL2 and ISG15 along with higher IFIT5. The rs2257167 CG/CC placentas also demonstrated high levels of IFIT5 and inflammation-related genes. InterpretationWe found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the IFNAR1 rs2257167 genotype. These findings shed light on the host-pathogen interaction focusing on the genetically regulated type I / type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections. FundingThis work was supported by the Instituto Oswaldo Cruz (Rio de Janeiro, Brazil) and by the Instituto de Tecnologia em Imunobiologicos (Rio de Janeiro, Brazil). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSLevels of type I and type III interferons are genetically controlled and decisively regulate outcome of spontaneous viral infections or response to antiviral treatment. Hepatitis C virus, Yellow Fever and Zika virus belong to the Flaviviridae family and elicit similar host immune responses. Congenital Zika Syndrome presents well-known risk factors, mainly the first trimester of pregnancy as well as social and nutritional factors, however, these do not entirely explain abnormal outcomes. Added value of this studyWe conducted a case-control study to evaluate SNPs in type I and III interferon genes using samples from newborns and mothers who had zika infection during pregnancy. We have shown that newborn interferon type I background contributes to the development of abnormal CSZ. This specific genetic makeup regulates placental immunological responses and prevents an exacerbated type I, and lack of type III, interferon response in syndromic cases. Implications of all the available evidenceOur study suggests an important factor regulating the host-pathogen interaction during Zika virus (ZIKV) infections in humans. During pregnancy, genetic variations play a role in balancing tissue-specific type I and III interferons during ZIKV congenital infection influencing fetal neurological damage. Custom pharmacological interventions could be used to modulate immunity and inflammation towards protective responses. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/715862v3_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@ee554forg.highwire.dtl.DTLVardef@122c773org.highwire.dtl.DTLVardef@547695org.highwire.dtl.DTLVardef@13543db_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2019

The discriminant pattern of pleural fluid inflammatory mediators between tuberculosis and other causes of exudative pleural effusion

Pleural tuberculosis (PlTB), a form of extrapulmonary TB, remains as a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon-gamma (IFN-{gamma}), IFN-{gamma}-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically or not confirmed cases) among other etiologies. In this prospective cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 22) and non-PlTB (NTB; n= 17) patients. The levels of IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-{gamma}, TNF, IP-10, TGF-{beta}1, and ADA were measured and a principal component analysis was applied in order to identify the mediators who contributed most for the variance in data. IFN-{gamma}, IP-10, TNF, TGF-{beta}, and ADA quantified in PF showed significantly higher concentrations in PlTB patients when compared to NTB ones. When blood and PF were compared, we have identified significantly higher concentrations of IL-6 and IL-10 in PF, in both groups. TGF-{beta}, solely, showed significantly increased levels in PF and blood from PlTB when both clinical specimens were compared to NTB patients. Principal components analysis from PF revealed that the ADA, IP-10, TGF-{beta}, and IFN-{gamma} contributed most for the discriminatory capacity between TPlB and NTB. Our findings showed that important inflammatory mediators in PF may discriminate TB cases from other causes of exudative effusion, the main diseases considered in the differential diagnosis of PlTB.

immunology↗

bioRxiv2019

HIV-1 controllers exhibit an enhanced antiviral state characterized by overexpression of p21 and MCPIP1

Some multifunctional cellular proteins, as the monocyte chemotactic protein-induced protein 1 (MCPIP1) and the cyclin-dependent kinase inhibitor p21, have also shown to be able to modulate the cellular susceptibility to the human immunodeficiency virus type 1 (HIV-1). Several studies described that p21 is expressed at high levels ex vivo in cells from individuals who naturally control HIV-1 replication (HIC). The expression level of MCPIP1 in HIC was never described before, but a recent study in a model of renal carcinoma cells showed that MCPIP1 overexpression was associated with an increase of both p21 transcripts and proteins levels. Here, we explored the potential associations between MCPIP1 and p21 expression, as well as with cellular activation in HIC, sustaining undetectable (elite controllers - EC) or low (viremic controllers - VC) viral loads. We found a selective upregulation of MCPIP1 and p21 mRNA levels in PBMC from HIC compared with both ART- suppressed and HIV-negative control groups (P [≤] 0.02) and a strong positive correlation (r [≥] 0.57; P [≤] 0.014) between expressions of both transcripts independently of the VL, treatment condition and HIV status. The mRNA levels of p21, but not of MCPIP1, were positively correlated with activated CD4+ T cells levels in HIC and EC (r [≥] 0.53; P [≤] 0.017). In relation to the monocyte activation, the mRNA levels of both p21 (r = 0.74; P = 0.005) and MCPIP1 (r = 0.58; P = 0.040) were positively correlated with plasmatic levels of sCD14 only in EC. Multivariate analysis confirmed the association between MCPIP1 and p21 mRNA levels, and between the latter with the frequency of activated CD4+ T cells. These data show for the first time the simultaneous overexpression and positive correlation of MCPIP1 and p21 transcripts in the setting of natural suppression of HIV-1 replication in vivo. The positive correlation between MCPIP1 and p21 transcripts supports a common regulatory pathway connecting these multifunctional host factors and a possible synergistic effect on HIV-1 replication control. Pharmacological manipulation of these cellular proteins may open novel therapeutic perspectives to prevent HIV-1 replication and disease progression.

immunology↗

bioRxiv2019

Icosahedral viruses defined by their positively charged domains: a signature for viral identity and capsid assembly strategy

Capsid proteins often present a positively charged arginine-rich region at the N and/or C-termini that for some icosahedral viruses has a fundamental role in genome packaging and particle stability. These sequences show little to no conservation at the amino-acid level and are structurally dynamic so that they cannot be easily detected by common sequence or structure comparison. As a result, the occurrence and distribution of positively charged protein domain across the viral and the overall protein universe are unknown. We developed a methodology based on the net charge calculation of discrete segments of the protein sequence that allows us to identify proteins containing amino-acid stretches with an extremely high net charge. We observed that among all organisms, icosahedral viruses are especially enriched in extremely positively charged segments (Q [≥] +17), with a distinctive bias towards arginine instead of lysine. We used viral particle structural data to calculate the total electrostatic charge derived from the most positively charged protein segment of capsid proteins and correlated these values with genome charge arising from the phosphates of each nucleotide. We obtained a positive correlation (r = 0.91, p-value < 0001) for a group of 17 viral families, corresponding to 40% of all families with icosahedral structures described so far. These data indicated that unrelated viruses with diverse genome types adopt a common underlying mechanism for capsid assembly and genome stabilization based on R-arms. Outliers from a linear fit pointed to families with alternative strategies of capsid assembly and genome packaging.\n\nSignificance StatementViruses can be characterized by the existence of a capsid, an intricate proteinaceous container that encases the viral genome. Therefore, capsid assembly and function are essential to viral replication. Here we specify virus families with diverse capsid structure and sequence, for each capsid packing capacity depends on a distinctive structural feature: a highly positively charged segment of amino acids residues, preferentially made of arginine. We also show that proteins with the same characteristics are rarely found in cellular proteins. Therefore, we identified a conserved viral functional element that can be used to infer capsid assembly mechanisms and inspire the design of protein nanoparticles and broad-spectrum antiviral treatments.

bioinformatics↗

bioRxiv2018

Natural avirulent Shigella boydii strain in the Brazilian Amazon lacks major virulence genes and present Type II, Type III and Type VI Secretion Systems

BackgroundAmong Shigella species, Shigella boydii has always displayed a smaller role to the overall Shigella burden, frequently placed at third in epidemiological studies and described as restricted to Southeast Asia. Here we characterize an S. boydii isolated from an epidemiological study enrolling 1,339 Brazilian children from the Amazon region, in which Shigella species solely was the fourth cause of bacterial diarrhea. S. boydii strain 183 was isolated from rotavirus co-infected children with acute diarrhea. Here we aimed to characterize this strain regarding virulence and, immune response in a pulmonary model.\n\nMethodsAn in vitro HEp-2 epithelial cell invasion assay was used to compare the invasive phenotype of S. boydii strain 183 with clinical and highly virulent S. flexneri strain, both isolated from Brazilian children. A murine pulmonary model was performed to assess lung damage by histopathological analysis. mRNA expression of immune response key genes was retrieved by multiplex real-time PCR and correlations were obtained by network analysis. Broad genome analysis was performed to confirm S. boydii identity and define its virulence profile.\n\nResultsS. boydii strain 183 showed fewer invasion rates in vitro and tissue damage in vivo as compared to virulent S. flexneri 201. When compared to a survival challenge in mice, S. boydii had 100% survival against 10% of virulent S. flexneri. Overall, mRNA immune gene expression suggests a protective response against S. boydii strains 183, in contrast to the inflammatory response induced by the virulent S. flexneri strain 201. Network analysis with S. boydii strain 183 displayed IFN-{gamma} protagonism, contrasting with the correlations centralized on TNF- by the virulent S. flexneri strain 201. The genome showed a lack of effector proteins and enterotoxins in S. boydii strain 183, and sequencing analysis of Ipa invasins revealed mutations at functional sites. This avirulent S. boydii strain 183 presents the Type II Secretion System, T6SS, in addition to T3SS.\n\nConclusionsIn addition to causing no disease, S. boydii strain 183 lacks effector proteins and enterotoxins. The presence of T6SS additional secretion system could provide an advantage to establish this strain among commensal bacteria.\n\nAUTHOR SUMMARYThe Shigella genus is a human pathogen responsible to shigellosis and remains one of the significant causes of morbidity and mortality in children under five years old. This genus has four species, Shigella flexneri, Shigella sonnei, Shigella boydii, and Shigella dysenteriae. S. flexneri and S. sonnei are the most common in the worldwide infections; S. dysenteriae is rarely found, and S. boydii is responsible for 1% of the infections and is known to be restricted to Southeast Asia. Once S. boydii have a relatively small role in global Shigella disease, there are few studies regarding its virulence and mechanisms. Here we characterize an S. boydii isolated from Brazilian children from the Amazon region, and aimed to describe this strain regarding virulence. It is known that Shigella species use the Type 3 Secretion System (T3SS) to invade and colonize the human intestine. We found in S. boydii the presence of Type 2 Secretion System (T2SS), Type 6 Secretion System (T6SS), in addition to the T3SS. The T6SS have been described in S. sonnei only, granting a competitive advantage against S. flexneri mixed cultures. The presence of T6SS additional secretion system could provide a benefit to establish this strain among commensal bacteria.

microbiology↗

bioRxiv2016

GeNNet: An Integrated Platform for Unifying Scientific Workflow Management and Graph Databases for Transcriptome Data Analysis

BackgroundThere are many steps in analyzing transcriptome data, from the acquisition of raw data to the selection of a subset of representative genes that explain a scientific hypothesis. The data produced may additionally be integrated with other biological databases, such as Protein-Protein Interactions and annotations. However, the results of these analyses remain fragmented, imposing difficulties, either for posterior inspection of results, or for meta-analysis by the incorporation of new related data. Integrating databases and tools into scientific workflows, orchestrating their execution, and managingthe resulting data and its respective metadata are challenging tasks. Running in-silico experiments to structure and compose the information as needed for analysis is a daunting task. Different programsmay need to be applied and different files are produced during the experiment cycle. In this context,the availability of a platform supporting experiment execution is paramount.\n\nResultsWe present GeNNet, an integrated transcriptome analysis platform that unifies scientific workflows with graph databases for selecting relevant genes according to the evaluated biological systems. GeNNet includes pre-loaded biological data, pre-processes raw microarray data and conducts a series of analyses including normalization, differential expression inference, clusterization and geneset enrichment analysis. To demonstrate the features of GeNNet, we performed case studies with data retrieved from GEO, particularly using a single-factor experiment. As a result, we obtained differentially expressed genes for which biological functions were analyzed. The results are integrated into GeNNet-DB, a database about genes, clusters, experiments and their properties and relationships.The resulting graph database is explored with queries that demonstrate the expressiveness of this data model for reasoning about gene regulatory networks.\n\nConclusionsGeNNet is the first platform to integrate the analytical process of transcriptome data with graph database. It provides a comprehensive set of tools that would otherwise be challenging for non-expert users to install and use. Developers as well can add new functionality to each component of GeNNet. The resulting data allows for testing previous hypotheses about an experiment as well as exploring new ones through the interactive graph database environment. It enables the analysis of different data on humans, rhesus, mice and rat coming from Affymetrix platforms.

bioinformatics↗