Animal studies begin for Chikungunya virus

By David Robson

- Last updated on GMT

Related tags: Infection, Virus

French scientists have found a suitable genetic variation of mice
that can be used to study the way the Chikungunya virus develops
and spreads in the human body.

Chikungunya has been responsible for epidemics in Africa, India and now Italy, and it is feared that the disease, which is transmitted through mosquito bites, may hit South America in the near future. The symptoms include fever, skin rashes, and pain in the patient's joints and muscles, and more severe cases can also affect the central nervous system. However, so far the way in which the virus infects the body is poorly understood, and current drugs can only treat the symptoms without attacking the underlying causes of the disease. Now, scientists at the Institut Pasteur and INSERM have found a genetically modified mouse that exhibits the same symptoms as a human when infected with the disease, which can be used to better understand the mechanisms behind the infection. The researchers have already been able to pinpoint areas where in the body the virus incubates and replicates, and it is hoped that the animal model could also be used to test potential vaccines and antiviral drugs. The researchers initially tried to infect unmodified mice with the disease, but they found that only the very young suffered from the disease, with adult mice seemingly unaffected. "We were faced with the problem that adult mice are not permissive to the disease, with a very low viral replication rate​," Marc Lecuit, one of the researchers, told To rectify this, the team tried to genetically modify the mice so they could not fight the infection so successfully. They achieved this by invalidating the receptor of the type 1 interferon protein - a key messenger protein that promotes the production of an antiviral response in the mouse's immune system. When one copy of the gene responsible for this receptor was deleted, the mice suffered from a milder form of the disease, and when two copies of this gene were deleted the mice suffered from the more severe form. By studying these mice, the team found that the virus initially infects the liver, where it replicates very rapidly. It then targets the muscles, skin and joints. "The organs where the pain is situated are also those which are infected. This may sound trivial, but with influenza this is not the case. This information explains the symptoms, and opens the question of why the virus affects this tissue​," said Lecuit. "Maybe it's a specific receptor in these cells that the virus attacks​." It is hoped that further studies with the mice will explain how the virus spreads from the muscle and skin tissue to the central nervous system in the more severe cases of the disease, and how the virus penetrates the placenta barrier when it is spread from mother to child. The team hope that the work may also help to explain how viruses are transmitted across tissue barriers for other diseases too. "We have a model, so we can now go into it and investigate all the details. And since we can reproduce the disease in an animal, we can treat the mice with antiviral drugs and vaccines to try to block the infection or alter the outcome​," he said. "The outcomes may be extremely important for the understanding of other infectious diseases​."

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