Rare Genetic Mutation Makes These Siblings Immune To Viruses

Rare Genetic Mutation Makes These Siblings Immune To Viruses

Viruses are incompetent but smart little things. Unable to make proteins on their own, they hijack ours for their own nefarious purposes. But what if we gave the viruses broken proteins? An incredibly rare genetic disorder in a brother and sister pair does exactly that, making them immune to many classes of viruses — and suggesting new possibilities for antiviral treatments.

The immunity to viruses for these siblings, however, comes at a cost. Their cases, reported recently in the New England Journal of Medicine, are only the second and third ever described of this rare genetic disorder. The first was in a baby who died at 74 days. The 11-year-old boy and six-year-old girl in this report have suffered developmental delays, hearing loss, fragile bones and a weakened immune system. That makes it all the more remarkable that they rarely got ear infections or the flu.

Their rare genetic mutation affects a basic biological process called glycosylation, when a sugar molecule is attached to something else, like a protein. These resulting sugar-proteins are used all over the body, and many viruses also hijack them to build a protective shell. Disrupting those sugar-proteins stops viruses, including those for influenza, herpes, dengue fever, hepatitis C and HIV. A notable exception would be adenoviruses, which cause the common cold.

Antiviral treatments might block glycosylation temporarily, to prevent viral infection without the devastating side effects. One drug that targets glycosylation is currently being tested in HIV patients, and it looks promising. “The worst side-effect was flatulence,” Dr Sergio Rosenzweig told NBC News, which seems like an acceptable proposition.

As for these kids, their genetic disorder is so rare, it’s still not well-understood. The other symptoms don’t seem clearly treatable. It does, however, provide, a unique window into understanding how the human body and viruses interact, opening the door to new drugs that may target other parts to the glycosylation process and treat other viral infections. It’s still far off, but these two kids could hold the eventual secret to fighting viruses. [NEJM via NBC News]


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