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November 30, 2022/Florida - Local

Cleveland Clinic Researchers Collaborate with International Team to Uncover How the Body Responds to Life-Threatening Disease from Herpes Simplex Virus 1

Researchers revealed novel genetic alterations and immune mechanisms in child hospitalized with herpes encephalitis

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WESTON, Fla. — A collaboration between Ghent University in Belgium and Cleveland Clinic’s Florida Research & Innovation Center (FRIC) found a new way genetics influences the body’s antiviral response by studying a life-threatening disease caused by a common virus: herpes simplex virus 1 (HSV-1).

The researchers analyzed genetic data from a patient with immunodeficiency and hospitalized at nine months old with herpes encephalitis, a rare but life-threatening brain inflammation after HSV-1 infection. They identified novel mutations in the gene GTF3A, and found that these mutations impair the innate immune response.

The findings, published in Science Immunology, hold potential as a genetic marker doctors could use to gauge a child’s risk of herpes encephalitis, although such mutations are generally very rare in the population.

Many people are infected in childhood with the HSV-1 virus but the vast majority don’t suffer from encephalitis. The most common symptom of HSV-1 is oral cold sores, but many people show no signs at all. HSV-1 is more threatening to children and adults who are immunodeficient, whose immune system cannot control the virus well.

Michaela Gack, Ph.D.

“Genetic and mechanistic analyses of uncommon viral diseases like herpes encephalitis are quite rare. In fact, the causes underlying severe herpes encephalitis are often unknown,” says Michaela Gack, Ph.D., FRIC’s scientific director. “This information provides us with invaluable insight into the fundamental molecular processes that govern our immune response and opens up opportunities for future research on severe disease outcomes.”

The Ghent research team led by Filomeen Haerynck, M.D., Ph.D., reached out to Dr. Gack’s team after finding the mutations in the gene. Dr. Gack’s lab studies interactions between the human immune system and viruses on a molecular level.

The GTF3A mutations shape how cells respond to viral activity through the genetic makeup of a protein called TFIIIA. TFIIIA plays a role in helping a human enzyme produce certain types of RNA that can determine specific functions inside cells. Some RNAs can elicit an anti-herpes viral immune response.

Dr. Gack’s team tested cells that have the mutations, and found that because of defects in certain immunostimulatory RNAs, the cells were more susceptible to HSV-1 infection and lost the ability to control the HSV-1 virus.

The affected gene is part of the body’s defense system that produces interferons to combat viruses. Interferons are crucial to the human immune response and for suppressing virus infection and spread.

This new genetic pathway could be helpful in understanding the immune response to other viruses, like Epstein-Barr virus, a common virus linked to mononucleosis and associated with certain types of cancer and multiple sclerosis.

“Understanding the molecular processes underlying antiviral responses is key to treating or possibly preventing severe viral infections that change patients’ and families’ lives,” Dr. Gack said. “Our findings on critical immune defense proteins may translate into new therapies in the future.”

The study was funded through U.S. National Institutes of Health grants AI165502 and AI087846, and the Flanders Institute for Biotechnology (VIB) Grand Challenges program. The award from VIB, an entrepreneurial non-profit research institute, is to the Ghent University.

About the Cleveland Clinic Florida Region

Cleveland Clinic’s regional health system in Florida region is a nonprofit, multi-specialty healthcare provider that integrates clinical and hospital care with research and education. The Florida region includes Cleveland Clinic Weston Hospital, Cleveland Clinic Indian River Hospital and Cleveland Clinic Martin Health and has five hospitals and numerous outpatient centers in Broward, Palm Beach, Martin, St. Lucie and Indian River Counties. The Florida region is an integral part of Cleveland Clinic in Ohio, where providing outstanding patient care is based upon the principles of cooperation, compassion and innovation. Physicians at Cleveland Clinic are experts in the treatment of complex conditions that are difficult to diagnose. For more information about Cleveland Clinic Florida, visit www.clevelandclinicflorida.org. Follow us on Twitter and Facebook.

About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 72,500 employees worldwide are more than 5,050 salaried physicians and researchers, and 17,800 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,500-bed health system that includes a 173-acre main campus near downtown Cleveland, 22 hospitals, more than 220 outpatient facilities, including locations in northeast Ohio; southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2021, there were 10.2 million total outpatient visits, 304,000 hospital admissions and observations, and 259,000 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic. News and resources available at newsroom.clevelandclinic.org.

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