Infección por el virus de la Lengua azul: activación de señales celulares que inducen apoptosis / Bluetongue virus infection: signaling pathway activated during apoptosis

El virus de la Lengua azul (VLA) es un ARN virus de doble cadena que induce apoptosis tanto en cultivos celulares como en tejidos blanco. Con el fin de dilucidar el mecanismo de apoptosis en la infección por el VLA, en el presente trabajo examinamos en detalle, por la técnica de Western blot, las señales celulares de caspasas, Bax, citocromo c, Smac/DIABLO y factor nuclear kappa B (NF-kB) que se activan en la infección viral. Hemos comprobado que luego de la infección in vitro con el VLA, se detectó la activación de la caspasa 8 y con ello el mecanismo extrínseco de la apoptosis. También detectamos por primera vez no sólo la activación de miembros de la familia Bcl-2 (Bax), sino también la liberación del citocromo c y la proteína Smac/DIABLO, confirmando que en la infección por el VLA está involucrado el mecanismo secuencial intrínseco de la apoptosis. Asimismo, demostramos que la infección por el VLA activa el NF-kB y que la apoptosis es sustancialmente reducida mediante la inhibición del mismo. La activación de las señales celulares tales como Bax, citocromo c, Smac/DIABLO y NF-kB presentados en este trabajo, esclarecen los mecanismos apoptóticos durante la infección por el VLA para una mayor comprensión del papel primario que juega la apoptosis en la patogénesis del virus.

Bluetongue (BTV) is a double-stranded RNA virus that induces apoptosis both in mammalian cell cultures and in target tissues. To elucidate the apoptosis pathways in BTV infection, we have examined in detail the apoptosis mechanism by examination of caspases, Bax, cytochrome c, Smac/DIABLO and NF-kB signalling pathways. In this report, after cell infection with BTV, the activation of caspase 8 was detected, proving the extrinsic receptor binding apoptotic pathway. Apoptosis followed a sequential pathway involving the detection of activated Bcl-2 family members. Furthermore, its translocation to the mitochondria, as well as the release of cytochrome c and Smac/Diablo confirmed that BTV apoptosis involves the sequential intrinsic pathway. In addition, we demonstrated that NF-kB was activated following BTV infection and cell treatment with an inhibitor peptide before BTV infection, prevented NF-kB activation and substantially reduced cellular apoptosis. Our accumulating data concerning the activation of Bax, cytochrome c, Smac/DIABLO and NF-kB clarify the mechanism of apoptosis during BTV infection, and confer a better understanding of the primary role of apoptosis in BTV pathogenesis.

Lengua Azul. Actualización sobre el agente y la enfermedad / Blue tongue. Update on the agent and the disease

Bluetongue (BT) is a viral disease of domestic and wild ruminants. It is particularly damaging in sheep, where up to half of infected animals may die, showing inflammation and hemorrhages of the mucous membranes of the mouth, nose, and intestines. In cattle and goats, BT rarely causes disease, however it can affect the animal's reproductive ability, so that losses are not easily estimated. Bluetongue virus spreads from animal to animal by biting insects of the genus Culicoides; and this is the reason why the disease is more prevalent in geographic areas where climate conditions are favourable for their development. The disease was first recognized in South Africa in the late 1700's, but it was not until the early 1900's that it was described in detail, and at present, epizootiology and pathogenesis studies are still being carried on.