Coevolution of host and virus: The pathogenesis of virulent and attenuatedstrains of myxoma virus in resistant and susceptible European rabbits

Myxoma virus was introduced into the European rabbit population of Australi a In 1950. Although the Virus was initially highly lethal in rabbits, there was rapid selection for less virulent strains of virus and innately resist ant rabbits. To investigate the basis of resistance to myxoma virus, we hav e compared the pathogensis of the virulent strain of myxoma virus originall y released into Australia and an attenuated, naturally derived field strain of myxoma virus. This was done in laboratory rabbits, which have not been selected for resistance, and in wild rabbits that have developed significan t resistance. Wild rabbits were able to recover from infection with virus t hat was always lethal in laboratory rabbits. Laboratory rabbits were able t o control and recover from infection with attenuated virus. This virus caus ed a trivial disease in wild rabbits. There was little difference between l aboratory and wild rabbits in titers of either virulent or attenuated virus in the skin at the inoculation site. However, resistant wild rabbits had a 10- to 100-fold lower titer of virulent virus within the lymph node draini ng the inoculation sire and controlled virus replication in tissues distal to the draining lymph node. Replication of virus in lymphocytes or fibrobla sts cultured from wild and laboratory rabbits demonstrated that resistance was not due to altered cellular permissivity for replication. Neutralizing antibodies were present in both susceptible and resistant rabbits, suggesti ng that these have no significant role in resistance. We hypothesise that r esistance is due to an enhanced innate immune response that allows the rabb it to mount an effective cellular immune response. (C) 2000 Academic Press.