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Genetic susceptibility in viral encephalitis

According to a study published in Science X-Press, an advanced, online edition of the journal Science on Sept. 14, a single gene immunodeficiency may cause susceptibility// to herpes simplex virus. This suggestion is contradictory to the current scientific theory of how genes function in vulnerability to infections. These findings may be relevant in other infectious diseases also.

In the study, scientists focused on blood cells from two French children with a deficiency for UNC-93B, an endoplasmic reticulum protein involved in the recognition of pathogens. When infected with herpes simplex virus-1, the UNC-93B-deficient cells were unable to produce natural interferons alpha, beta, and gamma (IFNs á, a and ?). Interferons are produced by the immune system to fight infections and tumors.

This deficiency resulted in high rates of herpes simplex virus-1 proliferation and cell death. Assuming these findings extend to neurons, they provide a plausible mechanism for herpes simplex encephalitis.

"We and our colleagues have identified recessive UNC-93B deficiency as a genetic etiology of herpes simplex encephalitis in otherwise healtalpha, ihy patients," said Professor Bruce Beutler, M.D., one of three Scripps Research scientists who contributed to the study. "The discovery of this genetic cause for herpes simplex encephalitis not only broadens our understanding of these types of immunodeficiencies, but also has important therapeutic implications-some of these patients could benefit from recombinant interferon alpha (IFN- á) treatment, just as patients with low levels of naturally occurring interferon gamma (IFN- ?) benefit from a similar life-saving approach."

Herpes simplex virus-1 is a common virus that infects about 80 percent of young adults worldwide. Herpes simplex encephalitis, a viral infection of the brain that affects otherwise healthy patients, affects an extremely small percentage of those infected with herpes simplex vir us-1: the number of annual cases is two per million people, according to the University of Maryland Medical Center.

Nonetheless, herpes simplex encephalitis, which was first described in 1941, is the most common type of sporadic viral encephalitis in developed countries, accounting for about 10 to 20 percent of all viral encephalitis cases, according to the University of Maryland Medical Center. Before the advent of anti-viral drugs vidarabine in 1973 and acyclovir in 1981, mortality rates reached up to 70 percent. While the introduction of anti-viral treatment has been a boon to patients, brain damage still poses a substantial risk.

"In contrast to most current thinking, we suspected that herpes simplex encephalitis susceptibility could be inherited as a monogenic trait resulting in the specific impairment of immunity to herpes simplex virus-1," Beutler said. "Here we have defined a genetic lesion that is permissive for an infection: a trait that most would regard as quintessentially environmental in cause. It is likely that other mutations will also be found to permit herpes simplex virus encephalitis, and likely that other infectious diseases will ultimately be traced to mutations that affect UNC-93B."

Source-Eurekalert
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