April 15, 2013

Mouse hepatitis virus may help end chimp research

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The deer mouse could replace chimps in work on a vaccine for hepatitis C (Image: Gerry Ellis/Minden Pictures/FLPA)

16:46 15 April 2013 by Sara Reardon

A newly discovered rodent virus that resembles hepatitis C could give research chimps a break.

The US National Institutes of Health (NIH) is expected to make a decision imminently on how many of its 360 research chimps should be retired on the grounds that most studies can be done in other animals. One exception, however, is research on the hepatitis C virus (HCV): chimps are the only species whose immune systems respond to HCV – which primarily affects the liver – in the same way as humans. But now it seems that working with a similar virus in deer mice could offer an alternative.

In 2011, partly in response to increasing pressure from activists, a US Institute of Medicine (IOM) panel issued a report concluding that most medical research using great apes is no longer justified. The report's summary said that researchers should avoid experiments on animals so closely related to humans unless the work is impossible to carry out in other animals or "is of sufficient scientific or health value to offset the moral costs".

The panel came to the conclusion that the vast majority of invasive biomedical studies did not fit these criteria, although some behavioral studies might. The NIH announced last year that it would accept the IOM's recommendations, and commissioned an outside panel to review ongoing US chimp studies. The panel found that three of the nine active biomedical research programmes were in line with the strict criteria, and recommended that the other six be shut down. NIH spokesperson Renate Myles said that the agency is reviewing comments from the public and will make a decision in coming months.

No consensus

However, the IOM panel was unable to reach a consensus on whether hepatitis C research in chimps should be allowed to go on. Vaccine development would be especially difficult without them, says Christopher Walker of Nationwide Children's Hospital in Columbus, Ohio, who is currently performing an HCV study in chimps.

Regardless of what the NIH decides, "I think everyone agrees that we need to reduce the use of chimps," says Ian Lipkin of Columbia University in New York. In addition to throwing up moral quandaries, working with great apes is expensive and difficult.

With this in mind, he and Amit Kapoor, also at Columbia, set out to find a smaller animal that could serve as a model for hepatitis C.

Using a DNA probe, they identified a set of variants based around one virus in deer mice that look genetically similar to HCV. The rodent viruses make the same proteins as HCV and are found in the animal's liver, suggesting that they could function in a similar way to HCV.

It's not yet clear whether the rodents' immune system responds when they are infected with the virus, or whether the virus mutates like it does in humans. Lipkin says the group hopes to have a mouse model within a year to start answering these questions.

Scope for manipulation

"This is something the hepatitis C field is in dire need of," says Stanley Lemon of the University of North Carolina in Chapel Hill, as it is very difficult to develop a vaccine without an animal model. A rodent virus is especially exciting as mice can be genetically manipulated to study how the immune system reacts to the virus.

Lipkin and Kapoor also have a paper in press describing the discovery of other HCV-like viruses in horses, bats and dogs. Comparing these with the human version could give hints as to how the virus mutates and causes disease, says Walker.

Could this be the end of chimps in HCV trials? "That's the hope," says Lipkin, but cautions that until the virus is proven to act in the same way as HCV in humans, it's too early to tell.

Journal reference: mBio, doi.org/k7p

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