HSV Infection Induces Production of ROS, which Potentiate Signaling from Pattern Recognition Receptors: Role for S-glutathionylation of TRAF3 and 6

The innate immune response constitutes the first line of defense against infections. Pattern recognition receptors recognize pathogen structures and trigger intracellular signaling pathways leading to cytokine and chemokine expression. Reactive oxygen species (ROS) are emerging as an important regulator of some of these pathways. ROS directly interact with signaling components or induce other post-translational modifications such as S-glutathionylation, thereby altering target function. Applying live microscopy, we have demonstrated that herpes simplex virus (HSV) infection induces early production of ROS that are required for the activation of NF-κB and IRF-3 pathways and the production of type I IFNs and ISGs. All the known receptors involved in the recognition of HSV were shown to be dependent on the cellular redox levels for successful signaling. In addition, we provide biochemical evidence suggesting S-glutathionylation of TRAF family proteins to be important. In particular, by performing mutational studies we show that S-glutathionylation of a conserved cysteine residue of TRAF3 and TRAF6 is important for ROS-dependent activation of innate immune pathways. In conclusion, these findings demonstrate that ROS are essential for effective activation of signaling pathways leading to a successful innate immune response against HSV infection

Anatomía de la arteria temporal superficial: importancia quirúrgica: estudio piloto en cadáveres

El conocimiento preciso de los patrones vasculares permite mejorar los resultados de la reconstrucción regional del pabellón auricular y el diseño de colgajos regionales dependientes de la arteria temporal superficial para la reconstrucción facial. En México, no contamos en la actualidad con descripciones anatómicas de las variantes vasculares normales de la arteria temporal superficial. El objetivo de este trabajo es la descripción de las variantes anatómicas de la arteria temporal superficial a través de la disección de este vaso en 12 regiones tempo-parieto-occipitales en cadáveres. Nuestros resultados muestran que la arteria temporal superficial siempre se divide en dos ramas, una anterior y otra posterior, la distribución de ésta se sitúa en el cuarto más posterior de la región temporal, con una bifurcación alta. La distribución de la anatomía vascular, tomando en cuenta el calibre mayor de la arteria temporal superficial con respecto a la arteria auricular posterior, la ausencia de esta última en 4 de las regiones estudiadas, así como la distancia de dichos vasos con respecto al conducto auditivo externo, sugieren que en nuestra población la irrigación del pabellón auricular depende de la arteria temporal superficial, restándole importancia a la aportación del riego sanguíneo de esta región por parte de la arteria auricular posterior. Nuestro estudio arroja resultados que indican la existencia de variaciones importantes en la anatomía vascular regional que justifican la realización de estudios posteriores que permitan una descripción mas detallada de la misma para aumentar el éxito de las intervenciones quirúrgicas

Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING

The innate immune system senses infection by detecting either evolutionarily conserved molecules essential for the survival of microbes or the abnormal location of molecules. Here we demonstrate the existence of a previously unknown innate detection mechanism induced by fusion between viral envelopes and target cells. Virus-cell fusion specifically stimulated a type I interferon response with expression of interferon-stimulated genes, in vivo recruitment of leukocytes and potentiation of signaling via Toll-like receptor 7 (TLR7) and TLR9. The fusion-dependent response was dependent on the stimulator of interferon genes STING but was independent of DNA, RNA and viral capsid. We suggest that membrane fusion is sensed as a danger signal with potential implications for defense against enveloped viruses and various conditions of giant-cell formation