Trapping WBC may be a novel strategy against chronic viral infections

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London, Aug 14 : Researchers at Yerkes National Primate Research Center and the Emory Vaccine Center have found that trapping disease-fighting white blood cells (WBC) in the lymph nodes might be a novel strategy against chronic viral infections, such as hepatitis C and HIV/AIDS.

Senior author John Altman, PhD, associate professor of microbiology and immunology at Yerkes Research Center and Emory University School of Medicine, said that the discoveries are based on the study of two varieties of a virus that causes meningitis in mice.

Standard black laboratory mice can fight off infection by the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), but are vulnerable to chronic infection by a variant called clone 13.

Altman and his colleagues found that infecting mice with the Armstrong strain sequesters white blood cells in the lymph nodes, while clone 13 does so less stringently.

"Our hypothesis was that if we could artificially induce conditions like those produced by the Armstrong strain, it would help the immune system clear an infection by clone 13," Nature quoted Altman, as saying.

The researchers turned to an experimental drug called FTY720, which prevents white blood cells from leaving lymph nodes.

FTY720, also known as fingolimod, desensitizes white blood cells so they can't respond to the chemical messenger sphingosine-1-phosphate (S1P).

S1P also influences heart rate and smooth muscle contraction in the airways.

Altman said that the scientists had previously thought of FTY720 as something that suppresses the immune system.

While not approved for sale by the FDA, doctors have tested it for the treatment of multiple sclerosis and preventing kidney transplant rejection.

The researchers found that even if mice have a stable chronic LCMV clone 13 infection, treatment with FTY720 can still improve their immune response against LCMV enough to have them rid it from their systems.

FTY720 appears to prevent "exhaustion" in the group of white blood cells called CD8+ T cells, which are responsible for killing off other cells that become infected by LCMV.

Altman said that usually, the stress of infection kills some CD8+ T cells and leaves others unable to respond to the virus.

He said that it is unclear whether FTY720 resuscitates non-responsive T cells or allows new ones to avoid being killed off.

The study is published in the journal Nature.

ANI

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