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UAM (Universidad Autónoma de Madrid)

UAM (Universidad Autónoma de Madrid)

La Universidad Autónoma de Madrid es una universidad pública española, ubicada en Madrid y fundada en 1968, momento en que sus facultades estaban dispersas por diversos edificios de la capital española. En junio de 2018 la Universidad Autónoma de Madrid cumplirá sus primeros 50 años. Para celebrar este aniversario, la universidad prepara un programa conmemorativo que se desarrollará entre los años 2016 y 2019 e incluirá actividades abiertas a todo el conjunto de la sociedad. https://www.uam.es/

Nuevas claves para entender la resistencia del VIH a los fármacos antirretrovirales

Fuente: UAM Gazette | Publicado: 05-02-2018
Investigadores del Centro de Biología Molecular Severo Ochoa, centro mixto de la Universidad Autónoma de Madrid (UAM) y el CSIC, han logrado identificar diferencias entre el VIH-1 y el VIH-2 que permiten entender cómo aparece la resistencia a los fármacos antirretrovirales más utilizados frente a estos virus.
Derechos: Vista del centro activo de la retrotranscriptasa mostrando cambios estructurales que se asocian con resistencia a fármacos antirretrovirales.
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Un estudio liderado desde el Centro de Biología Molecular Severo Ochoa –centro mixto de la Universidad Autónoma de Madrid (UAM) y el CSIC–, en el que también participan investigadores del Hospital Universitario Germans Trías i Pujol (Badalona) y la Universidad Francisco de Vitoria (Madrid), podría ayudar a mejorar los tratamientos contra el VIH y prevenir la aparición de resistencia.



Los resultados, publicados en el Journal of Biological Chemistry, ponen de manifiesto diferencias en las estructuras de las retrotranscriptasas del VIH-1 y el VIH-2, que resultan clave en la adquisición de resistencia a fármacos antirretrovirales muy utilizados en la clínica, como AZT, tenofovir o emtricitabina.


“Las retrotranscriptasas son proteínas necesarias para la multiplicación del VIH, ya que son las encargadas de sintetizar copias del material genético del virus”, explica Luis Menéndez Arias, director del estudio. “Actualmente, sus inhibidores constituyen la base de los tratamientos antirretrovirales. Los más importantes, conocidos como análogos a nucléosido, incluyen fármacos clásicos como el AZT y otros más utilizados en la actualidad, como el tenofovir”, agrega el investigador.


Inhibidores análogos a nucleósido

Los fármacos análogos a nucleosido son eficaces tanto para combatir al VIH-1 como al VIH-2. La retrotranscriptasa del VIH incorpora estos fármacos en la cadena de ADN, bloqueando la síntesis del material genético del virus.  A nivel molecular, los virus resistentes adquieren mutaciones que impiden que su retrotranscriptasa reconozca e incorpore los fármacos al ADN. Este mecanismo ocurre tanto en el VIH-1 como en el VIH-2 y se relaciona con la aparición de mutaciones tales como K65R, Q151M o M184V.

Sin embargo, hay un segundo mecanismo por el que la retrotranscriptasa de los virus resistentes ha adquirido la capacidad de eliminar el fármaco después de haberlo incorporado en el ADN viral. En el VIH-1, las mutaciones relacionadas con este mecanismo son M41L, D67N, K70R y T215Y.  Sin embargo, en el VIH-2, estos cambios son raros y casi nunca aparecen juntos en virus de pacientes infectados y tratados con fármacos análogos a nucleósido.



“Durante años se ha especulado mucho acerca de por qué en el VIH-2 no se observaban estas mutaciones. Nuestro trabajo demuestra que la retrotranscriptasa del VIH-2 es incapaz de desarrollar resistencia por el mecanismo de eliminación debido a la existencia de dos pequeños cambios en su secuencia de aminoácidos en las posiciones 73 y 75”, explica Luis Menéndez.


“Estos resultados –añade el investigador– fueron posibles tras un estudio detallado y exhaustivo que incluye la caracterización de más de 20 retrotranscriptasas con distintas combinaciones de mutaciones”.

Para los autores resulta sorprendente que ningún trabajo anterior haya sugerido el papel de la metionina-73, residuo clave para entender el mecanismo molecular implicado. “Aunque se trata de un estudio de investigación básica, la presencia de los cambios de aminoácido descritos en el trabajo podría tener importancia para la prescripción de tratamientos antirretrovirales adecuados”, concluyen.


Resistencia del VIH

Según la Organización Mundial de la Salud, hay alrededor de 37 millones de personas infectadas por el VIH en todo el mundo y cerca de 21 millones reciben tratamiento antirretroviral.

 A medio-largo plazo, la aparición de resistencia constituye una amenaza muy seria para el éxito de las terapias anti-VIH.  Se cree que el VIH-2 podría estar infectando a 1 o 2 millones de personas en todo el mundo, aunque la evidencia clínica demuestra que su evolución a SIDA es más lenta que con el VIH-1.

Sin embargo, muchos de los fármacos utilizados para tratar infecciones causadas por el VIH-1 no funcionan con el VIH-2, entre ellos algunos fármacos inhibidores de la retrotranscriptasa, como los llamados “no análogos a nucleósido”, cuyo representante más conocido es el efavirenz.


Referencia bibliográfica: Álvarez, M., Nevot, M., Mendieta, J., Martínez, M.A. y Menéndez-Arias, L. (2018). Amino acid residues in HIV-2 reverse transcriptase that restrict the development of nucleoside analogue resistance through the excision pathway. J. Biol. Chem. Doi:10.1074/jbc.RA117.000177.
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    Does maternity style make different demands of you, bag-wise? Does it have an effect on your bag choices? Coach Teigen always carries great bags, and the only change I see in her habits is that these bags are.fuzzier.

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    The Dime Bag is his biggest debut for spring, and its most notable featuree a key element from his Balenciaga days: a coiled wire top handle, similar to that of the Balenciaga Cable Bag. That bag wasn't a huge hit, unfortunately, and I doubt this one will be either.

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    Coach logo (tweaked to spell out COACH, of course), layered atop the geometric Fs.Special treats are featured within: Coach Teigen, a double dose of Hilary Duff, Lupita Nyong'o, and more Kardashians and Jenners than you have time to complain about!

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    At one of LA's most paparazzi-friendly restaurants, Madeo, Julie Chen and husband Les Moonves had dinner; Julie carried a Valentino Rockstud Spikes Clutch. Shop the Valentino Rockstud Spikes Clutch via Neiman Marcus ($1,545)

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    The most notable exception to that general rule is when the party in question is thrown by a handbag brand, which is the case with a Dior fete in Los Angeles earlier this week. Today, we're going to check out those bags, as well as a handful of other notable carries.

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    and also, let's be real, because February and early March are not big times for online designer discounts. But today we're back, and given a few weeks to refresh themselves, we found some awesome buys. Like, 50% off.

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    Check out our selections and the reasoning behind them below, and then let us know what you think in the comments.

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    Coach, Tod's, Balenciaga and that range from brand new to nearly vintage. There's mystery bags! There's even your favorite mom/aunt from film and/or television, Laurie Metcalf! Shall we dive in?

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