Thank you for your kind letter, the newspaper copies and other attached documents concerning rabbit calicivirus disease.

As you very rightly pointed out this disease is generally known in Europe as rabbit haemorrhagic disease (RHD) or viral haemorrhagic disease (VHD) and its causative agent, rabbit haemorrhagic disease virus (RHDV).

In the first place I must admit that I was very surprised by the number and type of most of your questions, which clearly indicate that you are very concerned about RCD. Consequently, I am afraid that some of my answers might disappoint you.

My contribution to the "60 Minutes" program was very brief but I believe I have made clear that we ignore more than we know about the virus and the disease it causes.

As you will see,most of your questions have not a clear answer yet or have not been investigated.

You ask if RHDV is a stable virus. Considering the type of genetic material of RHDV, the virions will tend to incorporate more changes in their genomes than other types of viruses (ie. the myxoma virus).Nevertheless not all the genetic changes will confer new properties to the virus (ie changes in virulence or host range). We know the complete genetic information of four independent isolates of RHDV from Germany, France, Italy and Spain, which shows a high level of similarity. Nevertheless, considering that they were all obtained in 1989 this does not allow to say much about its stability and how different they are with respect to the strains circulating now in the continent.

As you might know the initial descriptions of the disease showed that young animals (under two months of age) were not affected by the virus. Also,the virus had the capacity of aglutinating red blood cells, and this property was used to detect and quantify the virus. In the last two years some virus strains no longer aglutinate red blood cells and have gained the capacity to kill young rabbits.These are the types of changes I have mentioned in "60 Minutes". Right now, we are studying these new type of viruses trying to correlate the observed behaviour modifications and the genetic changes we have found. I am afraid this will take some time before we reach to a conclusion. As you see the virus is not totally stable.

You should consider also that RHD was described for the first time in 1984 and we have not previous reports of a pathology of this kind. This is telling us that either RHDV had a non pathogenic ancestor, which suddenly became virulent, or that RHDV jumped from another animal species. Both possibilities are rather intriguing and also point out that RHDV might not be as stable as we wish. Either of these events happened 12 years ago. There are some data supporting the non-pathogenic ancestor hypothesis.

Concerning the RHDV especificity to European Rabbits, I have not seen many published evidences indicating the type of experiments performed to demonstrate this fact.As you say the rabbit calicivirus could infect another species and that would not necessarily mean that it would die or suffer a pathology that we can notice.

When you inject a foreign substance into an animal (i.e. an organ extract containing RHDV) the host immune system normally reacts producing antibodies against it (seroconversion).This fact does not mean that the virus did proliferate in the injected animal. To demonstrate that the virus is able to infect the cells and produce a viral progenie (causing disease or not) you should do something else than measuring the presence or antibodies. The type of techniques to be used are difficult to explain but rely on the capacity of detecting either infective virions or genetic material from the virus in biological samples taken from the animal. To my knowledge nobody has reported the kind of experiments they have used to rule out infection. They just say the virus did not produce disease.

On the other hand if you detect antibodies in an animal that has not been experimentally injected (i.e.a wild animal) it is very difficult to assume seroconversion without infection of the cells and viral replication, unless the animal has been exposed several times to the virus. For instance a fox might develop anti-RHDV antibodies after eating infected rabbits several times. This again will need to be investigated further to see if the fox was in fact infected and not just immuno-stimulated by something in the food. As you see it is rather complex to demonstrate that viral infection had occurred, in the absence of pathological signs.

As far as I know no specific testing for anti-RHVD antibodies of rabbit handlers, veterinarians, scientists etc..have been reported.

How and why RHDV kills rabbits? We ignore the virulence factor that makes RHDV so lethal. It is not clear also the mechanism of infection and the type of susceptible cells. From our experience the virus can be transmited by air (does not need specific vectors). I can not say the range of temperature stability of the virus, although it should be rather stable because it consists of a cote, made of a single type of protein, enclosing the genetic material. This type of viruses, lacking lipids in their virions, are very resistant to ambient conditions. I guess extreme temperatures will inactivate RHDV.