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Sofía Bernal-Silva

Bio: Sofía Bernal-Silva is an academic researcher from Universidad Autónoma de San Luis Potosí. The author has contributed to research in topics: Genotype & Peripheral blood mononuclear cell. The author has an hindex of 5, co-authored 17 publications receiving 115 citations. Previous affiliations of Sofía Bernal-Silva include Oklahoma State University Center for Health Sciences.

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TL;DR: Although the PBMC from TB patients do not show apparent abnormalities in the expression of P2X7, and the intracellular signals generated through it, the pattern of gene expression induced by ATP in these cells is different from that found in healthy contacts.
Abstract: P2X7 is a channel receptor gated by adenosine triphosphate (ATP) that is involved in the killing of intracellular mycobacteria. To explore further the role of P2X7 in immunity against Mycobacterium tuberculosis, we studied its expression and function in 19 patients with pulmonary tuberculosis (TB) and 19 healthy contacts. Flow cytometry analysis showed a similar and variable expression of P2X7 in TB patients and healthy subjects. In contrast, P2X7 mARN levels were significantly higher in TB patients. When the function of the P2X7 receptor in peripheral blood mononuclear cells (PBMC) was assessed by the effect of exogenous ATP on apoptosis, the uptake of the fluorescent marker Lucifer yellow or extracellular signal regulated kinase (ERK) phosphorylation, no significant differences were detected in patients and controls. However, mRNA macroarray analysis showed that upon stimulation with ATP, the PBMC from TB patients showed a significant induction of a higher number of cytokine genes (27 of 96), and a lower number of apoptosis genes (20 of 96) compared to healthy controls (17 and 76 genes, respectively). These results suggest that although the PBMC from TB patients do not show apparent abnormalities in the expression of P2X7, and the intracellular signals generated through it, the pattern of gene expression induced by ATP in these cells is different from that found in healthy contacts. This phenomenon suggests a defective function of P2X7 in the immune cells from TB patients, a condition that may contribute to the inability of these patients to eliminate the mycobacteria.

31 citations

Journal ArticleDOI
TL;DR: ON1 strains include viruses that appear to be the result of at least 3 independent duplication events, and molecular data of strains from diverse geographical regions should help define the frequency and implications of this evolution mechanism.
Abstract: Background Respiratory syncytial virus (RSV) is a leading cause of respiratory infections. An RSV-A genotype (ON1) that contains a 72-nt duplication was reported in 2012 and has since extended worldwide. Methods We analyzed 345 respiratory samples obtained between 2003 and 2014 to assess the relevance of ON1 infections. Nucleotidic and deduced amino acid sequences from viruses detected in San Luis Potosi and sequences previously reported were analyzed. Results RSV ON1 was detected in 105 samples. The earliest case of ON1 infection was detected in November 2009, almost 1 year prior to detection of this virus in Canada. Amino acid sequence analysis of the duplication region showed the presence of Y273N and L274P substitutions in RSV GA2 viruses that, when combined, resulted in 4 different GXXSPSQ sequence motifs at positions 272-278. Three of these motifs were present in both the original and duplicated regions of ON1 strains. Additional signature amino acid substitutions were observed in ON1 strains that have the different sequence motifs. Conclusions ON1 strains include viruses that appear to be the result of at least 3 independent duplication events. Molecular data of strains from diverse geographical regions should help define the frequency and implications of this evolution mechanism.

30 citations

Journal ArticleDOI
TL;DR: The ICU admission rate and mortality rate in Mexican infants hospitalized with RSV infection were 5.2% and 1%, respectively, which was higher in infants <6 months of age than in other age groups.
Abstract: BACKGROUND Respiratory syncytial virus (RSV) is the most common etiology for acute respiratory infection hospital admissions in young children. Case fatality rates for hospitalized patients range between 0% and 3.4%. Recent reports indicate that deaths associated with RSV are uncommon in developed countries. However, the role of this virus as a current cause of mortality in other countries requires further examination. METHODS Children with RSV infection admitted between May 2003 and December 2014 to a level 2 specialty hospital in Mexico were included in this analysis. Underlying risk factors, admission to the intensive care unit (ICU) and condition on discharge were assessed to determine the ICU admission and death rates associated to RSV infection. RESULTS We analyzed data of 1153 patients with RSV infection in whom information regarding underlying illnesses and discharge status was available. Sixty patients (5.2 %) were admitted to the ICU and 12 (1.04 %) died. Relevant underlying conditions were present in 320 (27.7%) patients. Infants with underlying respiratory disorders (excluding asthma) and a history of prematurity had high ICU admission rates (17.1% and 13.8%, respectively). Mortality rates were highest for infants with respiratory disease (excluding asthma) (7.3%), cardiovascular diseases (5.9%) and neurologic disorders (5.3%). The ICU admission and death rates were higher in infants <6 months of age than in other age groups. CONCLUSIONS The ICU admission rate and mortality rate in Mexican infants hospitalized with RSV infection were 5.2% and 1%, respectively. Mortality rates were high in infants with respiratory, cardiovascular and neurologic disorders.

23 citations

Journal ArticleDOI
TL;DR: A phylogenetic analysis of 4,353 RSV-A G gene ectodomain sequences and the results indicate that previously reported genotypes can be classified into nine distinct genotypes: GA1-GA7, SAA1, and NA1.
Abstract: Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infections, is classified in two major groups (A and B) with multiple genotypes within them. Continuous changes in spatiotemporal distribution of RSV genotypes have been recorded since the identification of this virus. However, there are no established criteria for genotype definition, which affects the understanding of viral evolution, immunity, and development of vaccines. We conducted a phylogenetic analysis of 4,353 RSV-A G gene ectodomain sequences, and used 1,103 complete genome sequences to analyze the totallity of RSV-A genes. Intra- and intergenotype p-distance analysis and identification of molecular markers associated to specific genotypes were performed. Our results indicate that previously reported genotypes can be classified into nine distinct genotypes: GA1-GA7, SAA1, and NA1. We propose the analysis of the G gene ectodomain with a wide set of reference sequences of all genotypes for an accurate genotype identification.

17 citations

DOI
01 Nov 2021
TL;DR: A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.28.4) and 20B/P.
Abstract: Understanding the evolution of the SARS-CoV-2 virus in various regions of the world during the Covid-19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A real-time quantitative PCR screening and phylogenomic reconstructions directed at sequence/structure analysis of the spike glycoprotein revealed mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show spike protein mutations in the N-terminal domain (i.e. R190M), in the receptor-binding motif (i.e. T478K, E484K), within the S1-S2 subdomains (i.e. P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of single nucleotide variants from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades. Our results highlight the dual and complementary role of spike and nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage.

10 citations


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TL;DR: In neuroinflammatory and neurodegenerative diseases, P2X7 upregulation and function appears to contribute to disease progression, and is highlighted as a potential target to treat inflammatory related diseases.
Abstract: Under physiological conditions, adenosine triphosphate (ATP) is present at low levels in the extracellular milieu, being massively released by stressed or dying cells. Once outside the cells, ATP and related nucleotides/nucleoside generated by ectonucleotidases mediate a high evolutionary conserved signaling system: the purinergic signaling, which is involved in a variety of pathological conditions, including inflammatory diseases. Extracellular ATP has been considered an endogenous adjuvant that can initiate inflammation by acting as a danger signal through the activation of purinergic type 2 receptors-P2 receptors (P2Y G-protein coupled receptors and P2X ligand-gated ion channels). Among the P2 receptors, the P2X7 receptor is the most extensively studied from an immunological perspective, being involved in both innate and adaptive immune responses. P2X7 receptor activation induces large-scale ATP release via its intrinsic ability to form a membrane pore or in association with pannexin hemichannels, boosting purinergic signaling. ATP acting via P2X7 receptor is the second signal to the inflammasome activation, inducing both maturation and release of pro-inflammatory cytokines, such as IL-1β and IL-18, and the production of reactive nitrogen and oxygen species. Furthermore, the P2X7 receptor is involved in caspases activation, as well as in apoptosis induction. During adaptive immune response, P2X7 receptor modulates the balance between the generation of T helper type 17 (Th17) and T regulatory (Treg) lymphocytes. Therefore, this receptor is involved in several inflammatory pathological conditions. In infectious diseases and cancer, P2X7 receptor can have different and contrasting effects, being an angel or a demon depending on its level of activation, cell studied, type of pathogen, and severity of infection. In neuroinflammatory and neurodegenerative diseases, P2X7 upregulation and function appears to contribute to disease progression. In this review, we deeply discuss P2X7 receptor dual function and its pharmacological modulation in the context of different pathologies, and we also highlight the P2X7 receptor as a potential target to treat inflammatory related diseases.

271 citations

Journal ArticleDOI
TL;DR: A historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding is provided.
Abstract: This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5′-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells.

230 citations

Journal Article
TL;DR: In this paper, the authors used a mouse model of cytomegalovirus infection to show that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100fold in the spleen and 1,000-fold in liver after infection.
Abstract: In an adaptive immune response, naive T cells proliferate during infection and generate long-lived memory cells that undergo secondary expansion after a repeat encounter with the same pathogen. Although natural killer (NK) cells have traditionally been classified as cells of the innate immune system, they share many similarities with cytotoxic T lymphocytes. We use a mouse model of cytomegalovirus infection to show that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100-fold in the spleen and 1,000-fold in the liver after infection. After a contraction phase, Ly49H-positive NK cells reside in lymphoid and non-lymphoid organs for several months. These self-renewing 'memory' NK cells rapidly degranulate and produce cytokines on reactivation. Adoptive transfer of these NK cells into naive animals followed by viral challenge results in a robust secondary expansion and protective immunity. These findings reveal properties of NK cells that were previously attributed only to cells of the adaptive immune system.

194 citations

Journal ArticleDOI
TL;DR: The results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries.

180 citations