Rinderpest and peste des petits ruminants: a future treatment centring on interfering RNA

In regions with a large animal production sector, the viruses that cause these diseases – of the genus Morbillivirus – have significant repercussions on the local economy and food security: in Senegal, the economic impact of a peste des petits ruminants focus was estimated in 1996 at 80 000 euros over three months.

Rinderpest affects domestic cattle, buffaloes and yaks, but also sheep, goats and some pig races, along with a whole range of wild species. Despite a sustained blanket preventive vaccination campaign that has almost wiped out the disease on a global level, there are still some persistent infection foci in the Somali ecosystem. And there is no cure. As regards peste des petits ruminants, which affects sheep and goats, it is found in Africa, on the Arabian Peninsula, in the Middle East and in India. The available preventive vaccines are effective, but still have some drawbacks, such as their low heat resistance. There is no therapeutic treatment against this disease either.

Since early 2005, CIRAD has been developing a new control method against these diseases, based on a novel technique derived from molecular genetics. This new approach centres on a natural biological mechanism: “RNA interference”, which usually allows multicellular organisms to control the level of expression of some of their genes. The process involves short RNA fragments capable of preventing the reading and translation into proteins of the genetic code carried by DNA: the fragments are known as interfering RNA. They prevent the RNA playing its fundamental role as a messenger of the information contained in the genes with a view to protein production. In effect, so-called interfering RNA links specifically to the target messenger RNA, resulting in the latter's deterioration and consequently inhibiting expression of the corresponding protein.

Interfering RNA inhibits more than 80% of virus replication

CIRAD researchers have recently identified three synthetic interfering RNAs capable of inhibiting more than 80% of peste des petits ruminants and rinderpest virus replication in vitro. They are targeted at the messenger RNA of the nucleoprotein gene of the viruses that cause the diseases, blocking the virus multiplication process. An application was made for a patent on the results concerning these new biological antivirals in December 2005.

The second phase of the research has now begun: in vivo tests of the new generation of antivirals on infected animals. To this end, the plan is to transfer the interfering RNA to infected animals through a viral vector generally used as a vaccine. If this is indeed seen to inhibit virus replication in the diseased animals, this would open the way for the development of therapeutic vaccines against rinderpest and peste des petits ruminants. The work is due to last for five years, and should make it possible to provide farmers with a safe, effective vaccine.

The results look very promising, and open up vast prospects in terms of animal health. They could be of interest for other viruses such as bird flu or African swine fever. For this last disease, using RNA interference as a control method would be a major step forward, as there is not currently any preventive vaccine.