Descubren mecanismo que permite al virus de la Influenza evadir la respuesta inmune del organismo

Investigadores de la Universidad de California del Sur (USC) han identificado un mecanismo molecular crucial que permite al virus de la Influenza evadir la respuesta del sistema inmune del organismo. El estudio será publicado el 21 de mayo en la revista Cell Host & Microbe.
“Hemos encontrado un mecanismo que el virus de la influenza emplea para inhibir la respuesta inmune del organismo y que enfatiza en el papel crítico que juega cierta proteína en la defensa contra virus,” dijo Jae Jung, Ph.D, investigador principal del estudio. “Conjuntamente con nuestros estudios anteriores (Nature, 2007 y PNAS, 2008) este hallazgo puede brindar a los investigadores la información necesaria para crear un nuevo medicamento para reforzar la inmunidad y bloquear la infección y replicación del virus de la Influenza.”
http://www.medicalnewstoday.com/articles/150928.php

Several specific intracellular receptors are responsible for detecting the virus and activating the body’s defensive mechanisms. When a virus’ RNA enters the intracellular fluid, a receptor known as retinoic-acid-inducible gene I (RIG-I) detects it and triggers a response that limits virus replication and calls the body’s defenses into action. RIG-I acts as the sensor and security force against attacks, Jung explains. Then, a protein known as TRIM25 helps RIG-I transmit an alarm signal, which ultimately floods the cell and surrounding tissue with antiviral interferons.

The influenza virus is highly infectious and poses a serious and sometimes deadly health risk because of its ability to mutate into new strains and spread quickly during seasonal epidemics, as seen in the recent outbreak of the H1N1 swine flu virus, Jung says.

Researchers have long been working to understand how respiratory influenza is able to slip past the body’s innate immune responses. They have found that the influenza A virus has evolved by incorporating Non-structural protein 1 (NS1) into its genome to escape the RIG-I alarm system.

This process is one reason why the virus kills an average of 36,000 people every year. In fact, the 1918 “Spanish flu” pandemic influenza virus, which killed over 40 million people worldwide, muted the RIG-I response and interferon activity much more efficiently than contemporary flu viruses, Jung notes.

“Despite the conceptual linking of RIG-I with flu virus NS1, however, the precise mechanism has been unclear for a long period of time,” he says.

By studying the immune responses of animal models, researchers found that the influenza A virus NS1 attacks TRIM25, inhibiting its ability to assist RIG-I trigger the alarm system against the virus. Remarkably, a flu virus carrying an NS1 mutant defective for this activity loses its virulence in animal models, Jung says.

“We now know that the influenza virus escapes recognition via the interaction of NS1 with TRIM25, which inhibits the body’s immune response,” he says. “Understanding this host-virus interaction is an essential step in developing safe and effective drugs to target the influenza virus.”

This work was performed in collaboration with Adolfo Garcia-Sastre, Ph.D., at Mt. Sinai Medical School and the final doctorate experiments of Michaela Gack, Ph.D., who is the paper’s first author and currently a faculty member at Harvard Medical School.