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RNA Treatment Tested for West Nile Virus

Aedes albopictus mosquito

Aedes albopictus mosquito, one of those responsible for spreading West Nile virus (CDC.gov)

30 March 2018. A therapy for West Nile Virus made with interfering RNA molecules is shown in lab mice to reduce viral loads, including in the brain where the disease can do serious damage. The treatments and findings by a team from Yale University in New Haven, Connecticut are described in yesterday’s issue of the journal Cell Host & Microbe (paid subscription required).

West Nile virus appears in the in the U.S. during the summer and fall and is spread by infected birds, who then spread the virus to mosquitoes, and on to humans bitten by infected mosquitoes. Most people with the virus experience at worst mild symptoms including fever, headache, body aches, nausea, vomiting, and sometimes swollen lymph glands or a skin rash. Some of those affected, however, develop more severe symptoms, such as coma or paralysis that can last several weeks and lead to permanent neurological damage. Centers for Disease Control and Prevention says more than 2,100 cases of West Nile virus were reported in the U.S. during 2016, including some 1,300 cases affecting the nervous system.

Researchers led by virologist and infectious disease specialist Priti Kumar are seeking treatments for West Nile virus, where so far no treatments nor vaccines are approved. Kumar’s lab studies gene therapies, particularly where RNA transcribed from genetic codes in DNA can limit or block production of proteins that cause infections. In this case, the Yale team devised a treatment based on short interfering RNA,  or siRNA, used in gene therapies to silence specific genes.

To treat West Nile virus cases that affect the brain, however, the researchers needed to take further steps to cross the blood-brain barrier. This barrier of tightly packed cells lining blood vessels prevents most molecules from crossing from the blood stream into brain cells, which keeps out foreign substances, but also keeps out most drugs to treat neurological conditions. To bypass this barrier, the researchers encased the interfering RNA molecules in a peptide known as RVG9R, derived from rabies viruses and can enter nerve cells in the brain. The team also formulated the treatments to be administered through the nose, which reduces the distance to brain cells.

The researchers tested the treatments in lab mice in late stages of infection with West Nile virus, also affecting their brain cells. Of the mice given the treatments, 90 percent survived after 5 or 6 days, while mice given a placebo formula died within 10 days. The team also found mice receiving the test treatments cleared the virus from their brains, and generated a long-term immune response.

Since the nasal anatomy in mice is different from humans, the researchers say the treatments still need more work. Nonetheless, the authors conclude nasal-administered RNA treatments are a promising strategy for treating West Nile and similar types of flaviviruses affecting the nervous system, possibly including the Zika virus.

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