Virus Del Chikungunya: Características Virales Y Evolución Genética

El virus Chikungunya pertenece al género Alphavirus de la familia de los Togaviridae. Es transmitido por artrópodos, en particular por la picada de especies de mosquitos tales como Aedes aegypti y Aedes albopictus. El curso clínico característico de la infección incluye fiebres, artralgias y exantema. Desde que fue reportado en 1952 en los límites de Tanzania y Mozambique, ha generado brotes de enorme significado epidemiológico. Recientemente, fue causado un brote en las Américas por una cepa del virus, aparentemente, asiática. En la presente revisión presentamos su filogenia, estructura y organización del genoma. Enfatizaremos en el mecanismo de multiplicación y la expresión genética. Finalmente, la interacción virus-huésped y sus mecanismos de adaptación a vectores específicos también son discutido

A new pipeline for structural characterization and classification of RNA-Seq microbiome data

Background High-throughput sequencing enables the analysis of the composition of numerous biological systems, such as microbial communities. The identification of dependencies within these systems requires the analysis and assimilation of the underlying interaction patterns between all the variables that make up that system. However, this task poses a challenge when considering the compositional nature of the data coming from DNA-sequencing experiments because traditional interaction metrics (e.g., correlation) produce unreliable results when analyzing relative fractions instead of absolute abundances. The compositionality-associated challenges extend to the classification task, as it usually involves the characterization of the interactions between the principal descriptive variables of the datasets. The classification of new samples/patients into binary categories corresponding to dissimilar biological settings or phenotypes (e.g., control and cases) could help researchers in the development of treatments/drugs. Results Here, we develop and exemplify a new approach, applicable to compositional data, for the classification of new samples into two groups with different biological settings. We propose a new metric to characterize and quantify the overall correlation structure deviation between these groups and a technique for dimensionality reduction to facilitate graphical representation. We conduct simulation experiments with synthetic data to assess the proposed method’s classification accuracy. Moreover, we illustrate the performance of the proposed approach using Operational Taxonomic Unit (OTU) count tables obtained through 16S rRNA gene sequencing data from two microbiota experiments. Also, compare our method’s performance with that of two state-of-the-art methods. Conclusions Simulation experiments show that our method achieves a classification accuracy equal to or greater than 98% when using synthetic data. Finally, our method outperforms the other classification methods with real datasets from gene sequencing experiments

Exploring the secrets of virus entry: the first respiratory syncytial virus carrying beta lactamase

BackgroundRespiratory Syncytial Virus (RSV) presents a significant health threat, especially to young children. In-depth understanding of RSV entry mechanisms is essential for effective antiviral development. This study introduces an innovative RSV variant, featuring the fusion of the beta-lactamase (BlaM) enzyme with the RSV-P phosphoprotein, providing a versatile tool for dissecting viral entry dynamics.MethodsUsing the AlphaFold2 algorithm, we modeled the tertiary structure of the P-BlaM chimera, revealing structural similarities with both RSV-P and BlaM. Functional assessments, utilizing flow cytometry, quantified beta-lactamase activity and GFP expression in infected bronchial epithelial cells. Western blot analysis confirmed the integrity of P-BlaM within virions.ResultsThe modeled P-BlaM chimera exhibited structural parallels with RSV-P and BlaM. Functional assays demonstrated robust beta-lactamase activity in recombinant virions, confirming successful P-BlaM incorporation as a structural protein. Quercetin, known for its antiviral properties, impeded viral entry by affecting virion fusion. Additionally, Ulixertinib, an ERK-1/2 inhibitor, significantly curtailed viral entry, implicating ERK-1/2 pathway signaling.ConclusionsOur engineered RSV-P-BlaM chimera emerges as a valuable tool, illuminating RSV entry mechanisms. Structural and functional analyses unveil potential therapeutic targets. Quercetin and Ulixertinib, identified as distinct stage inhibitors, show promise for targeted antiviral strategies. Time-of-addition assays pinpoint quercetin’s specific interference stage, advancing our comprehension of RSV entry and guiding future antiviral developments

Respiratory Syncytial Virus NS1 Protein Colocalizes with Mitochondrial Antiviral Signaling Protein MAVS following Infection

Respiratory syncytial virus (RSV) nonstructural protein 1(NS1) attenuates type-I interferon (IFN) production during RSV infection; however the precise role of RSV NS1 protein in orchestrating the early host-virus interaction during infection is poorly understood. Since NS1 constitutes the first RSV gene transcribed and the production of IFN depends upon RLR (RIG-I-like receptor) signaling, we reasoned that NS1 may interfere with this signaling. Herein, we report that NS1 is localized to mitochondria and binds to mitochondrial antiviral signaling protein (MAVS). Live-cell imaging of rgRSV-infected A549 human epithelial cells showed that RSV replication and transcription occurs in proximity to mitochondria. NS1 localization to mitochondria was directly visualized by confocal microscopy using a cell-permeable chemical probe for His6-NS1. Further, NS1 colocalization with MAVS in A549 cells infected with RSV was shown by confocal laser microscopy and immuno-electron microscopy. NS1 protein is present in the mitochondrial fraction and co-immunoprecipitates with MAVS in total cell lysatesof A549 cells transfected with the plasmid pNS1-Flag. By immunoprecipitation with anti-RIG-I antibody, RSV NS1 was shown to associate with MAVS at an early stage of RSV infection, and to disrupt MAVS interaction with RIG-I (retinoic acid inducible gene) and the downstream IFN antiviral and inflammatory response. Together, these results demonstrate that NS1 binds to MAVS and that this binding inhibits the MAVS-RIG-I interaction required for IFN production

Virus Del Chikungunya: Características Virales Y Evolución Genética

El virus Chikungunya pertenece al género Alphavirus de la familia de los Togaviridae. Es transmitido por artrópodos, en particular por la picada de especies de mosquitos tales como Aedes aegypti y Aedes albopictus. El curso clínico característico de la infección incluye fiebres, artralgias y exantema. Desde que fue reportado en 1952 en los límites de Tanzania y Mozambique, ha generado brotes de enorme significado epidemiológico. Recientemente, fue causado un brote en las Américas por una cepa del virus, aparentemente, asiática. En la presente revisión presentamos su filogenia, estructura y organización del genoma. Enfatizaremos en el mecanismo de multiplicación y la expresión genética. Finalmente, la interacción virus-huésped y sus mecanismos de adaptación a vectores específicos también son discutido

Salud Global / Global Health

Salud Global / Global Healt

Biología molecular del virus sincitial respiratorio y desarrollo de estrategias profilácticas

Resumen El virus sincitial respiratorio es uno de los patógenos con la más alta prevalencia en infecciones del tracto respiratorio superior e inferior. Este virus desencadena cuadros tan severos como bronquiolitis en los lactantes y neumonías en los ancianos. El desarrollo de vacunas se ha visto afectado por la falta de conocimiento respecto a cuál es el mecanismo inmunitario adecuado para prevenir la infec- ción, además de la capacidad del virus para interferir con el desarrollo de la respuesta inmunitaria. El objetivo es revisar la biología molecular del virus, cómo éste puede interferir con la respuesta inmunitaria y cómo este conocimiento previo ha servido para desarrollar estrategias profilácticas tipo vacunas que aunque todavía están en escala del laboratorio lucen prometedoras. La fuente de información para esta revisión fueron los artículos publicados desde 1990 hasta la fecha en las revistas indexadas en ISI y PUBMED. Palabras claves: Virus sincitial respiratorio, profilaxis, biología molecular, ciclo de infección/ SALUD UNINORTE. Barranquilla (Col.) 2006; 22 (2): 135-153 Abstract Respiratory syncytial virus is one of the pathogens with the highest prevalence in infections of upper and lower respiratory tracts. This virus triggers clinical phenotypes as severe as bronchiolytis in infants and pneumonia in the elderly. The development of vaccines has been hampered by the lack of knowledge regarding the adequate immune mechanism able to address the infection as well as the ability of the virus to interfere with the development of a complete immune response. The aim of this paper is to review the molecular biology aspects of the virus; how the virus is able to interfere with the immune response; and how this previous knowledge has helped us to develop prophylactic strategies as vaccines, which they look promising even though they are still at bench scale. The source for this review came from articles published from 1990 until today in journal indexed in ISI and PUBMED. Key words: Respiratory syncytial virus, prophylaxis, molecular biology, infection csycl

Protein Kinase C-α Activity Is Required for Respiratory Syncytial Virus Fusion to Human Bronchial Epithelial Cells

Respiratory syncytial virus (RSV) infection activates protein kinase C (PKC), but the precise PKC isoform(s) involved and its role(s) remain to be elucidated. On the basis of the activation kinetics of different signaling pathways and the effect of various PKC inhibitors, it was reasoned that PKC activation is important in the early stages of RSV infection, especially RSV fusion and/or replication. Herein, the role of PKC-α during the early stages of RSV infection in normal human bronchial epithelial cells is determined. The results show that the blocking of PKC-α activation by classical inhibitors, pseudosubstrate peptides, or the overexpression of dominant-negative mutants of PKC-α in these cells leads to significantly decreased RSV infection. RSV induces phosphorylation, activation, and cytoplasm-to-membrane translocation of PKC-α. Also, PKC-α colocalizes with virus particles and is required for RSV fusion to the cell membrane. Thus, PKC-α could provide a new pharmacological target for controlling RSV infection