Video Experimental Relacionado

Updated: May 9, 2026

Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.

Assessing the Innate Sensing of HIV-1 Infected CD4⁺ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.

Published on: September 1, 2015

La GMP-AMP sintasa cíclica es un sensor inmune innato del VIH y otros retrovirus

Daxing Gao¹, Jiaxi Wu, You-Tong Wu

¹Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.

Science (New York, N.Y.)

|August 10, 2013

Resumen

La adenosina monofosfato-guanosina monofosfato cíclica (cGAMP) sintasa (cGAS) actúa como un sensor inmune innato para el VIH y otros retrovirus. Este descubrimiento revela cómo el cuerpo detecta y responde a las infecciones virales.

Área de la Ciencia:

Inmunología Inmunología.
Virología Virología.
Biología Molecular Biología Molecular

Sus antecedentes:

Los retrovirus, como el VIH, desencadenan respuestas inmunes innatas, pero los sensores específicos del huésped involucrados siguen siendo en gran medida no identificados.
La inmunidad innata juega un papel crítico en el control de las infecciones virales, lo que requiere la identificación de los receptores de reconocimiento de patógenos.

Objetivo del estudio:

Para identificar el sensor del huésped responsable de detectar los retrovirus e iniciar la señalización inmune innata.
Para dilucidar el mecanismo molecular por el cual la infección retroviral activa la producción de citoquinas.

Principales métodos:

Investigó la activación de la sintasa (cGAS) del monofosfato de guanosina-adenosina monofosfato cíclico (cGAMP) y las vías STING en la infección por VIH.
Utilizó inhibidores de la transcriptasa inversa y la integrasa para determinar el estadio de la replicación viral que desencadena la respuesta inmune.
Empleó estrategias de nocaut y knockdown para el cGAS tanto en ratones como en líneas celulares humanas para evaluar su papel en la inducción de citoquinas.

Principales resultados:

Se demostró que la infección por VIH activa el cGAS, lo que lleva a la producción de cGAMP y la posterior activación de STING, induciendo interferones de tipo I y otras citocinas.
La inhibición de la transcriptasa inversa, pero no la integrasa, bloqueó la inducción de interferón-β, lo que indica que el ADN viral transcrito inverso es el desencadenante.
La interrupción de la función cGAS abrogó la inducción de citoquinas en respuesta al VIH, el virus de la leucemia murina y el virus de la inmunodeficiencia simiana.

Conclusiones:

La adenosina monofosfato-guanosina monofosfato cíclico (cGAMP) sintasa (cGAS) funciona como un sensor inmune innato clave para el VIH y los retrovirus relacionados.
Los hallazgos revelan una vía crítica para la detección retroviral, que involucra la señalización cGAS-STING, que es esencial para iniciar respuestas inmunes antivirales.

Más Videos Relacionados

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa

Published on: June 30, 2016

Videos de Conceptos Relacionados

Intracellular Signaling Cascades

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...

cAMP-dependent Protein Kinase Pathways

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

GPCRs Regulate Adenylyl Cylase Activity

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...

Global Regulatory Systems

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...

Activation and Inactivation of G Proteins

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...

Size and Structure of Viral Genomes

Size and Structure of Viral Genomes

Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...