How influenza evades the body's defenses
Photo by Mark Berndt
The study will be published in the May 21 issue of the journal Cell Host & Microbe.
“We have found a mechanism that the influenza virus uses to inhibit the body’s immune response that emphasizes the vital role of a certain protein in defending against viruses,”,” says Jae Jung, Ph.D., professor and chair of the Department of Molecular Microbiology and Immunology at the Keck School of Medicine of USC, and the principal investigator of the study. “Along with our previous studies (Nature 2007 and PNAS 2008), this finding could provide researchers with the information needed to create a new drug to enhance immunity and block influenza virus infection and replication.”
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.
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USC in the News
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The Chronicle of Higher Education mentioned USC’s $6 billion fundraising campaign. The story noted that USC had already raised $1 billion in a “quiet phase,” including the $200 million naming gift from USC Trustee and alumnus David Dornsife and wife Dana Dornsife to the USC Dornsife College.
The Guardian (U.K.) highlighted two major gifts to USC in a list of the 10 biggest philanthropic benefactors in America. The list included the $200 million naming gift from USC Trustee and alumnus David Dornsife and wife Dana Dornsife to the USC Dornsife College, and the $110 million gift from USC Trustee and USC Viterbi School alumnus John Mork and wife Julie to create the USC Mork Family Scholars Program.
The New York Times featured the USC U.S.-China Institute documentary “Assignment: China — The Week that Changed the World.” The documentary, part of a series, examines media coverage of the 1972 Nixon trip that reshaped U.S.-China relations after a quarter century of isolation and hostility. “People look back now and take it for granted that the outcome was preordained,” said the institute’s Mike Chinoy, who produced the documentary. Voice of America also featured the story.
Los Angeles Times featured the Oscar Senti-meter, a tool developed by the USC Annenberg School, Los Angeles Times and IBM that analyzes thousands of tweets about the Academy Awards nominees. The story noted that Mexican actor Demian Bechir received an enormous boost on Twitter the day of the nominations, with a total of 6,893 tweets mentioning him, a 47-fold increase from the day before. The story noted the tool uses language-recognition technology developed in collaboration with USC Viterbi School’s Signal Analysis and Interpretation Lab.
The Times of India (India) featured a three-day medical emergency training workshop organized in association with USC. At the workshop, held at GCS Medical College in India, 50 doctors and more than 100 paramedics learned how to improve emergency support systems. William Mallon of the Keck School of USC said that discussion topics included the use of portable ultrasonic devices to scan patients. “The ultrasound applications help physicians make accurate and timely decisions,” he noted. Daily News & Analysis (India) also featured the workshop.
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