Benign circulation of rabbit haemorrhagic disease virus on Lambay Island, Eire.

With the exception of virus strains Ashington and RCV, other recognised strains of Rabbit haemorrhagic disease virus (RHDV) share relatively close genetic homology. Using serology and phylogenetic analysis, we have identified a third disparate virus lineage in healthy rabbits on Lambay Island off the east coast of Eire, where disease due to RHDV has never been observed. ELISA tests revealed high titre RHDV-specific antibodies in 81% of the sera from 11 healthy rabbits captured on this island, indicating that the virus is actively circulating amongst these rabbits. Nevertheless, infectious virus has not been isolated from rabbits living on this island. The detection of antibodies and the disparate Lambay virus lineage in an apparently healthy and isolated wild rabbit population provides the most convincing evidence yet that at least some strains of RHDV can circulate harmlessly for long periods of time in wild rabbits possibly by producing persistent or latent infections.

Epidemiology of rabbit haemorrhagic disease virus in the United Kingdom: evidence for seasonal transmission by both virulent and avirulent modes of infection.

Rabbit haemorrhagic disease virus (RHDV) has killed many millions of wild rabbits in Europe and Australia, but has had little impact in the United Kingdom, despite outbreaks having occurred since 1994. High seroprevalence detected in the absence of associated mortality had suggested the presence of an endemic non-pathogenic strain which may be 'protecting' UK populations. Following the first detailed field study of RHDV epidemiology in the United Kingdom, using mark-recapture with serum sampling, we report that RHDV caused highly prevalent persistent infection in seropositive rabbits in the absence of associated mortality. Furthermore the virus strains responsible could not be distinguished phylogenetically from known pathogenic isolates, and were clearly very different from the only previously identified non-pathogenic strain of RHDV. These findings suggest that many--perhaps most--strains of RHDV may be propagated through both 'pathogenic' and 'non-pathogenic' modes of behaviour. Transmission occurred predominantly during and just after the breeding season.

Long-term survival of New Zealand rabbit haemorrhagic disease virus RNA in wild rabbits, revealed by RT-PCR and phylogenetic analysis.

Because Rabbit haemorrhagic disease virus (RHDV) is highly pathogenic for rabbits, farmers illegally introduced it as a bio-control agent onto New Zealand farms in 1997. The virus was dispersed rapidly, initially causing high fatality rates in rabbits. Nevertheless, many survived and these surviving rabbits have been investigated for evidence of infection by RHDV. Livers from healthy rabbits contained RHDV-specific RNA, as shown by nested RT-PCR sequencing. The sequences of the viral capsids were related closely to the released Czech strain of RHDV, although the sequence from one rabbit was related most closely to a Spanish strain of RHDV. Phylogenetic analysis of the capsid sequences of 38 samples implied that there have been at least two introductions of the Czech virus into New Zealand, probably corresponding firstly to the original illegal introduction by farmers and secondly to the introduction of the same virus under governmental control. Genomic length sequence of two samples was obtained, suggesting that they may have retained the potential to be infectious, although this has not yet been demonstrated. The detection of genomic-length RNA in the liver of healthy rabbits suggests that even though a highly virulent virus was introduced into New Zealand, it rapidly established persistent or latent infections in a proportion of rabbits. This might account for their ability to survive in the face of virulent released virus. Moreover, the co-circulation of other strains of RHDV in the same rabbit population, such as the Spanish strain, might also impact on their susceptibility to the bio-control agent.

Molecular epidemiology of Rabbit haemorrhagic disease virus.

Millions of domestic and wild European rabbits (Oryctolagus cuniculus) have died in Europe, Asia, Australia and New Zealand during the past 17 years following infection by Rabbit haemorrhagic disease virus (RHDV). This highly contagious and deadly disease was first identified in China in 1984. Epidemics of RHDV then radiated across Europe until the virus apparently appeared in Britain in 1992. However, this concept of radiation of a new and virulent virus from China is not entirely consistent with serological and molecular evidence. This study shows, using RT-PCR and nucleotide sequencing of RNA obtained from the serum of healthy rabbits stored at 4 degrees C for nearly 50 years, that, contrary to previous opinions, RHDV circulated as an apparently avirulent virus throughout Britain more than 50 years ago and more than 30 years before the disease itself was identified. Based on molecular phylogenetic analysis of British and European RHDV sequences, it is concluded that RHDV has almost certainly circulated harmlessly in Britain and Europe for centuries rather than decades. Moreover, analysis of partial capsid sequences did not reveal significant differences between RHDV isolates that came from either healthy rabbits or animals that had died with typical haemorrhagic disease. The high stability of RHDV RNA is also demonstrated by showing that it can be amplified and sequenced from rabbit bone marrow samples collected at least 7 weeks after the animal has died.

The emergence of rabbit haemorrhagic disease virus: will a non-pathogenic strain protect the UK?

Rabbit haemorrhagic disease virus emerged in China in 1984, and has killed hundreds of millions of wild rabbits in Australia and Europe. In the UK there appears to be an endemic non-pathogenic strain, with high levels of seroprevalence being recorded, in the absence of associated mortality. Using a seasonal, age-structured model we examine the hypothesis that differences in rabbit population demography differentially affect the basic reproductive rates (R(0)) of the pathogenic and non-pathogenic strains, leading to each dominating in some populations and not others. The strain with the higher R(0) excluded the other, with the dynamics depending upon the ratio of the two R(0) values. When the non-pathogenic strain dominated, the pathogenic strain caused only transient mortality, although this could be significant when the two R(0) values were similar. When the pathogenic strain dominated, repeated epidemics led to host eradication. Seroprevalence data suggest that the non-pathogenic strain may be protecting some, but not all UK populations, with half being 'at risk' from invasion by the pathogenic strain and a fifth prone to significant transient mortality. We identify key questions for empirical research to test this prediction.

Susceptibility of wild rabbits (Oryctolagus cuniculus) in the United Kingdom to rabbit haemorrhagic disease (RHD).

Adult wild rabbits from the southern UK, previously unexposed to rabbit haemorrhagic disease (RHD), were experimentally challenged with a UK strain of the virus in laboratory conditions. Initial serum antibodies were measured by an haemagglutination inhibition test and all seropositive rabbits, with reciprocal titres > 10, were protected against fatal infection. These results are consistent with the behaviour of laboratory and commercially bred rabbits in similar circumstances, and are relevant to consideration of the overall impact of RHD in wild populations.

Does myxomatosis still regulate numbers of rabbits (Oryctolagus cuniculus Linnaeus, 1758) in the United Kingdom?

Myxomatosis now kills a much smaller proportion of rabbit populations than in the past, while remaining an important regulatory factor, as shown experimentally. On two separate occasions, experimental reduction of the prevalence of the disease (by reducing infestations of the main vector, the rabbit flea) led to significant increases in numbers of rabbits surviving the winter.

Myxomatosis: population dynamics of rabbits (Oryctolagus cuniculus Linnaeus, 1758) and ecological effects in the United Kingdom.

In 1953-1955, myxomatosis spread among rabbits (Oryctolagus cuniculus) in the United Kingdom, causing 99% mortality. Subsequently, there was a gradual increase in rabbit numbers. By 1955, the Ministry of Agriculture, Fisheries and Food (MAFF) had already found attenuated strains of myxoma virus. By 1970, genetic resistance had appeared. In the 1970s, mortality declined to 47-69% with only approximately 25% of rabbits infected, giving a field mortality of 12-19%. However, myxomatosis is persistent, generally showing a major prevalence peak in autumn and often a minor peak in spring. An eight-year MAFF experiment in which prevalence of the disease was artificially reduced indicates that myxomatosis remains a significant factor in population regulation. After rabbit numbers fell in the 1950s, important ecological changes took place: vegetation altered due to reduced grazing pressure, predators were affected by the reduction of a major prey species and these changes also affected many other animals. Currently, rabbit numbers have returned to approximately one-third of pre-myxomatosis levels and this is causing damage to farm and conservation habitats.