Australian Wild Rabbits Research Articles

Fifty-year review: European rabbit fleas,

European rabbit fleas were released among Australian wild rabbits in the late 1960s to supplement mosquitoes as vectors of myxoma virus. Data from study sites across southern Australia in the 1960s and 1970s are reviewed to discern common elements of flea-borne myxomatosis epizootics and a simple model is proposed to explain how virus virulence and food quality interact to determine rabbit abundance. Low, stable populations of rabbits implied that, despite virus attenuation and increased rabbit disease resistance, flea-borne myxomatosis was extremely important in controlling rabbit populations. Despite the enhancement of myxomatosis, livestock producers benefitted little from the additional pasture because marketing difficulties were not conducive to industry growth. Native wildlife likely benefitted, nonetheless.

Retrospective serological analysis reveals presence of the emerging lagovirus RHDV2 in Australia in wild rabbits at least five months prior to its first detection.

The lagovirus rabbit haemorrhagic disease virus (RHDV) has been circulating in Australia since the mid-1990s when it was released to control overabundant rabbit populations. In recent years, the viral diversity of different RHDVs in Australia has increased, and currently four different types of RHDV are known to be circulating. To allow for ongoing epidemiological studies and impact assessments of these viruses on Australian wild rabbit populations, it is essential that serological tools are updated. To this end, reference sera were produced against all four virulent RHDVs (RHDV, RHDV2 and two different strains of RHDVa) known to be present in Australia and tested in a series of available immunological assays originally developed for the prototype RHDV, to assess patterns of cross-reactivity and the usefulness of these assays to detect lagovirus antibodies, either in a generic or specific manner. Enzyme-linked immunosorbent assays (ELISAs) developed to detect antibody isotypes IgM, IgA and IgG were sufficiently cross-reactive to detect antibodies raised against all four virulent lagoviruses. For the more specific detection of antibodies to the antigenically more different RHDV2, a competition ELISA was adapted using RHDV2-specific monoclonal antibodies in combination with Australian viral antigen. Archival serum banks from a long-term rabbit monitoring site where rabbits were sampled quarterly over a period of 6years were re-screened using this assay and revealed serological evidence for the arrival of RHDV2 in this population at least 5months prior to its initial detection in Australia in a dead rabbit in May 2015. The serological methods and reference reagents described here will provide valuable tools to study presence, prevalence and impact of RHDV2 on Australian rabbit populations; however, the discrimination of different antigenic variants of RHDVs as well as mixed infections at the serological level remains challenging.

RHDV2 overcoming RHDV immunity in wild rabbits (Oryctolagus cuniculus) in Australia

THE emergence of rabbit haemorrhagic disease (RHDV) virus 2 (RHDV2) in Europe (Le Gall-Recule and others 2011) has been associated with declines in wild rabbit ( Oryctolagus cuniculus ) populations...

Increased virulence of rabbit haemorrhagic disease virus associated with genetic resistance in wild Australian rabbits (Oryctolagus cuniculus)

The release of myxoma virus (MYXV) and Rabbit Haemorrhagic Disease Virus (RHDV) in Australia with the aim of controlling overabundant rabbits has provided a unique opportunity to study the initial spread and establishment of emerging pathogens, as well as their co-evolution with their mammalian hosts. In contrast to MYXV, which attenuated shortly after its introduction, rapid attenuation of RHDV has not been observed. By studying the change in virulence of recent field isolates at a single field site we show, for the first time, that RHDV virulence has increased through time, likely because of selection to overcome developing genetic resistance in Australian wild rabbits. High virulence also appears to be favoured as rabbit carcasses, rather than diseased animals, are the likely source of mechanical insect transmission. These findings not only help elucidate the co-evolutionary interaction between rabbits and RHDV, but reveal some of the key factors shaping virulence evolution.

Recovery of South Australian rabbit populations from the impact of rabbit haemorrhagic disease

Context Recovery of Australian rabbit populations from the impact of rabbit haemorrhagic disease virus (RHDV) contrasts with more prolonged suppression of wild rabbits in Europe, and has been widely discussed in the scientific community, but not yet documented in formal scientific literature. The underlying causes of recovery remain unclear, but resistance to RHDV infection has been reported in laboratory studies of wild-caught rabbits. Aims We document numerical changes in two South Australian wild rabbit populations that were initially suppressed by RHDV, and examine serological data to evaluate several alternative hypotheses for the cause of recovery. Methods Rabbit numbers were assessed from spotlight transect counts and dung mass transects between 1991 and 2011, and age and RHDV antibody sero-prevalence were estimated from rabbits shot in late summer. Key results Rabbit numbers were heavily suppressed by RHDV between 1995 and 2002, then increased 5- to 10-fold between 2003 and 2010. During the period of increase, annual RHDV infection rates remained stable or increased slightly, average age of rabbits remained stable and annual rainfall was below average. Conclusions Rabbit populations recovered but neither avoidance of RHDV infection, gradual accumulation of long-lived RHD-immune rabbits, nor high pasture productivity were contributing factors. This leaves increased annual survival from RHDV infection as the most likely cause of recovery. Implications Previously documented evidence of resistance to RHDV infection may be of little consequence to post-RHD recovery in rabbit numbers, unless the factors that influence the probability of infection also shape the course of infection and affect survival of infected rabbits.

In situ hybridisation assay for localisation of rabbit calicivirus Australia-1 (RCV-A1) in European rabbit (Oryctolagus cuniculus) tissues

Recently, a new lagovirus enzootic in Australian wild rabbits was identified and described as rabbit calicivirus Australia-1 (RCV-A1). Unlike the closely related Rabbit Haemorrhagic Disease Virus (RHDV), which causes fulminant hepatitis and rabbit death, RCV-A1 does not appear to induce any clinical disease. RCV-A1 has been postulated to act as an imperfect natural vaccine to RHDV thus reducing RHDV-induced rabbit mortality, which is detrimental for bio-control of rabbits in Australia. This study was carried out to determine in which cells RCV-A1 replication occurs. An in situ hybridisation (ISH) protocol was developed using a RCV-A1 specific probe to localise the virus in rabbit tissues. The results were compared to those obtained with a quantitative RT-PCR assay that had previously been developed to measure RCV-A1 RNA in rabbit tissues. The histology of the tissues was also examined. ISH showed that virus replication, inferred by the presence of detectable RNA, was limited to a small number of epithelial cells towards the tip of the villi in the duodenum. Quantitative RT-PCR detected RCV-A1 RNA in jejunum, ileum and lymphoid tissue at day 3, 4 and 7 post-infection, but no hybridisation was detected in these tissues.

A sensitive and specific blocking ELISA for the detection of rabbit calicivirus RCV-A1 antibodies

BackgroundAntibodies to non-pathogenic rabbit caliciviruses (RCVs) cross-react in serological tests for rabbit hemorrhagic disease virus (RHDV) and vice versa, making epidemiological studies very difficult where both viruses occur. It is important to understand the distribution and interaction of the two viruses because the highly pathogenic RHDV has been used as a biocontrol agent for wild rabbits in Australia and New Zealand for the past 17 years. The presence of the benign RCV Australia 1 (RCV-A1) is considered a key factor for the failure of RHDV mediated rabbit control in cooler, wetter areas of Australia.ResultsA highly sensitive and specific blocking ELISA was developed for the detection of RCV-A1 antibodies. When sera from rabbits with a known infection history for either RCV-A1 or RHDV were tested, this assay showed 100% sensitivity and no cross-reactivity with RHDV sera (100% specificity).ConclusionsThis new ELISA not only allows the detection of RCV-A1 at a population level, but also permits the serological status of individual rabbits to be determined more reliably than previously described methods. This robust and simple to perform assay is therefore the tool of choice for studying RCV-A1 epidemiology in Australian wild rabbit populations.

The effect of rabbit population control programmes on the impact of rabbit haemorrhagic disease in south‐eastern Australia

Summary 1. The effect of rabbit population density on transmission of rabbit haemorrhagic disease virus (RHDV) is a critical aspect of disease ecology for rabbit control and rabbit conservation. We examined the interaction between rabbit control and spread of RHDV and a non‐pathogenic calicivirus (bCV) in Australian wild rabbit populations, and reviewed existing recommendations for control in this context. 2. Rabbits were sampled at eight pairs of sites; from rabbit populations where densities had been reduced by conventional control and from matching uncontrolled populations. Sites chosen ranged from hot, arid areas where RHDV had greatly reduced rabbit numbers to cooler, higher‐rainfall areas where rabbits remained more abundant. Virus activity was implied from antibody profiles in sera of surviving rabbits. 3. Reducing population density by conventional control had a similar effect on disease transmission despite a seven‐fold difference in initial density. Populations reduced by 70% or more had lower RHDV antibody prevalence in juvenile rabbits but not in adult rabbits, indicating that reducing rabbit density slowed but did not stop RHDV transmission. We found no interactions between rabbit control, RHDV and bCV that could be exploited to improve rabbit management. 4. Synthesis and applications. Delayed RHDV infection in rabbit control sites is likely to be offset by higher mortality in older rabbits, so that conventional rabbit control does not reduce the impact of RHDV on rabbit populations. Only minor changes to delay the timing of summer rabbit control programmes in cooler areas of Australia are necessary to take best advantage of RHDV‐induced reduction in rabbit numbers. For conservation management of rabbits in Europe, these findings indicate that RHDV may continue to have a severe impact on rabbit populations that have been reduced to low population density, but also raise the possibility that bCVs might be introduced to rabbit populations to aid their recovery.

The non-pathogenic Australian lagovirus RCV-A1 causes a prolonged infection and elicits partial cross-protection to rabbit haemorrhagic disease virus

Two caliciviruses occur in Australian wild rabbits: rabbit calicivirus Australia 1 (RCV-A1) and rabbit haemorrhagic disease virus (RHDV), which is used in Australia as a biocontrol agent to reduce feral rabbit populations. There is concern that RCV-A1 acts as a natural vaccine and protects from lethal RHDV infection. To investigate this hypothesis, domestic rabbits were perorally infected with RCV-A1, monitored for 28 days and subsequently challenged with RHDV. We show that RCV-A1 causes a non-pathogenic infection and is shed in faeces for up to 7 days post-infection. RCV-A1 was detected in the bile 2 months post-inoculation, indicating a prolonged or possible persistent infection. All animals infected with RCV-A1 developed antibodies cross-reacting to RHDV. When challenged with RDHV, half of the rabbits (n=4) survived the infection. The results indicate that RCV-A1 is likely to persist in rabbit populations and can elicit partial cross-protection to lethal RHDV infection.

Antibody status and survival of Australian wild rabbits challenged with rabbit haemorrhagic disease virus

In Australia, the epidemiology of rabbit haemorrhagic disease virus (RHDV) is complicated by non-pathogenic forms of calicivirus (bCV) co-circulating with RHDV and providing variable protection from RHDV. Currently no bCV virus-specific antibody tests exist; however, a series of four ELISAs used to detect antibodies to RHDV provided an indirect means to detect antibodies to bCV, enabling antibody categories of seronegative, maternal RHDV, RHDV or bCV to be determined. Rabbits (188) from four locations were challenged with RHDV and logistic regression models determined that, for rabbits <15 months old, survival was dependent on antibody titres alone and the relationship did not vary with age, capture site, gender, liveweight or reproductive status. All rabbits survived challenge after reaching 15 months of age, irrespective of their antibody titres. Where bCV antibodies were prevalent in young rabbits, the bCV category did not adequately summarise all information about rabbit survival that can be obtained from antibody titres. Within antibody categories, 95% of rabbits with RHDV, 33% with bCV, 40% with maternal RHDV and 22% with seronegative antibodies survived. The high survival rate of adults implies that natural outbreaks or controlled releases of RHDV will have little impact on adult breeding rabbits. Therefore, where RHDV and bCV are endemic, conventional rabbit-control programs targeting the immune breeding populations should provide the most predictable outcome for long-term maintenance of low rabbit populations.

Identification and partial characterisation of a new lagovirus in Australian wild rabbits

Rabbit Haemorrhagic Disease Virus (RHDV) is widely used in Australia to control feral rabbit populations. Before RHDV was released on the Australian continent in 1996, antibodies cross-reacting in RHDV specific ELISAs were found in Australian wild rabbits, leading to the hypothesis that a non-pathogenic calicivirus had been circulating in rabbit populations in Australia, potentially providing some level of cross-immunoprotection to RHDV infection. For the detection of this putative virus, a universal lagovirus PCR test was developed to screen a variety of different tissues of wild caught rabbits. We identified a new lagovirus in the intestinal tissues of three apparently healthy young wild rabbits. Quantitative Real Time PCR analysis revealed high concentrations of viral RNA in intestinal tissues and suggests a faecal-oral mode of transmission. Genome organisation and phylogenetic analysis following the sequencing of the entire viral genome revealed a new member of the genus Lagovirus within the family Caliciviridae.

Virulence and pathogenesis of the MSW and MSD strains of Californian myxoma virus in European rabbits with genetic resistance to myxomatosis compared to rabbits with no genetic resistance

The pathogenesis of two Californian strains of myxoma virus (MSW and MSD) was examined in European rabbits ( Oryctolagus cuniculus) that were either susceptible to myxomatosis (laboratory rabbits) or had undergone natural selection for genetic resistance to myxomatosis (Australian wild rabbits). MSW was highly lethal for both types of rabbits with average survival times of 7.3 and 9.4 days, respectively, and 100% mortality. Classical clinical signs of myxomatosis were not present except in one rabbit that survived for 13 days following infection. Previously described clinical signs of trembling and shaking were observed in laboratory but not wild rabbits. Despite the high resistance of wild rabbits to myxomatosis caused by South American strains of myxoma virus, the MSW strain was of such high virulence that it was able to overcome resistance. The acute nature of the infection, relatively low viral titers in the tissues and destruction of lymphoid tissues, suggested that death was probably due to an acute and overwhelming immunopathological response to the virus. No virus was found in the brain. The MSD strain was attenuated compared to previously published descriptions and therefore was only characterized in laboratory rabbits. It is concluded that Californian MSW strain of myxoma virus is at the extreme end of a continuum of myxoma virus virulence but that the basic pathophysiology of the disease induced is not broadly different to other strains of myxoma virus.

Statistical models for the effect of age and maternal antibodies on the development of rabbit haemorrhagic disease in Australian wild rabbits

Statistical models have been developed to explain the influence of age and maternal antibody on the outcome of rabbit haemorrhagic disease virus (RHDV) infection of Australian wild rabbit kittens in terms of survival, survival time in those that failed to survive, and pyrexia (temperature response, or fever). Similar models describing survival and survival time were derived by substituting mass for age, owing to their high correlation. The models were developed from data obtained following the inoculation of 78 kittens 5–11 weeks old born to does with varying levels of α-RHDV immunoglobulin (IgG) antibody as measured by enzyme-linked immunosorbent assay (ELISA). A significant correlation was found between survival and doe titre but not between survival and kitten titre. It was deduced that maternal antibody in kittens can fall below the level of detection in the ELISA but still be protective. The model describing the influence of age and doe titre had the form logit(SURVIVAL) = 5.98 – 0.944(AGE) + 0.000473(DOE TITRE), and showed, for example, that kittens born to seronegative does had a 50% probability of survival at about 6 weeks old and, with a doe titre of 10 240, a 50% probability of survival at about 11 weeks old. There was a significant influence of kitten titre on pyrexia, and the model developed had the form logit(TEMPERATURE RESPONSE) = 1.436 – 0.0531(KITTEN TITRE). The influence of age and maternal antibody on survival time was fitted using Cox proportional hazard models. A parametric regression gave rise to a final model of the form S(t | AGE, DOE TITRE) = exp[–(t/ηAGE)1.7979], where ηAGE = exp[7.1838 – 0.2976(AGE) + 0.000227(DOE TITRE)]. The model showed that survival time decreased with age, but for each age category there was an increase in survival time with increasing doe titre. Kitten titre had only a marginally significant effect on seroconversion; there was no effect of kitten age or mass, or of doe titre. No kitten with a titre of 60 or more seroconverted.

Serological evidence for the presence of a calicivirus in Australian wild rabbits, Oryctolagus cuniculus, before the introduction of rabbit haemorrhagic disease virus (RHDV): its potential influence on the specificity of a competitive ELISA for RHDV

The objective of the study was to determine for Australian wild rabbits the specificity of a competitive enzyme-linked immunosorbent assay (cELISA) developed in Italy for detecting antibodies to RHDV. Analysis of 657 sera collected before the arrival of RHDV (pre-RHD) indicated that between 17 and 38% appeared to give false positive results depending on the cut-off criteria used. The finding of pre-RHD sera reacting positively in the cELISA prompted the testing of sera in a cELISA using as antigen smooth forms of RHDV (cELISA-sf) and a solid-phase ELISA (spELISA), both of which detect reactivity to an epitope shared by the lagomorph caliciviruses. Testing of a subset of the pre-RHD sera in the cELISA-sf and the spELISA revealed that 86 and 91%, respectively, were positive. Similar results were obtained for a set of sera collected pre-RHD in the Australian Capital Territory (ACT). Sera collected from wild-stock rabbits born and raised in isolation in an animal house in the ACT were all negative in the cELISA, 6% were positive in the cELISA-sf and 13% in the spELISA. It was concluded that a calicivirus related to RHDV and European brown hare syndrome virus (EBHSV) was present in the rabbit population before the arrival of RHDV, and may still be present. The potential consequences of these findings for epidemiological studies on RHD in Australia are discussed.

Efficacy of a competitive enzyme-linked immunosorbent assay (cELISA) for estimating prevalence of immunity to rabbit haemorrhagic disease virus (RHDV) in populations of Australian wild rabbits (Oryctolagus cuniculus)

This study examines the efficacy of a cELISA in estimating the prevalence of immunity to rabbit haemorrhagic disease virus (RHDV) in wild rabbits in Australia. Rabbits (n = 343) captured from six locations in Victoria and Queensland were experimentally challenged with a lethal oral dose (1500 50%-lethal doses, LD50) of RHDV. Death or survival to challenge was used to determine the performance characteristics of the test. The diagnostic specificity, sensitivity and accuracy were highly variable between sites, making it difficult to select a representative cut-off value for all sites that achieved a reasonable level of accuracy for the prediction of surviving and non-surviving rabbits. Estimates of prevalence of immunity were biased owing to effects of site of capture (time of capture) and age structure of the population. Using predictive equations, the best estimates of survival were ±10% but these results came from a limited range of sites, all of which had survival in the range 49–70%. The cELISA will determine whether the RHDV is present in rabbit populations but it should be used with caution when estimating the prevalence of immunity to RHDV. The cELISA may thus be limited in its application for examining the epidemiology of RHDV in Australian rabbit populations.

Factors affecting the survival of Australian wild rabbits exposed to rabbit haemorrhagic disease

Rabbit haemorrhagic disease virus (RHDV) is foreign to Australia, and first entered populations of Australian wild rabbits (Oryctolagus cuniculus L.) in Australia in late 1995. Rabbits are serious environmental and agricultural pests in Australia, and RHDV, a major new pathogen, was introduced as a biological control agent to reduce their numbers. Our study evaluated some of the factors affecting survival of wild rabbits exposed to rabbit haemorrhagic disease (RHD) at 78 sites across Australia.Our data on rabbit numbers consist of the number of rabbits per spotlight kilometre present shortly before and shortly after an RHD outbreak at each site. They are a direct measure of survival rather than mortality. By reducing the interval between the pre- and post-RHD counts to the minimum possible, we sought to minimise the influence on the analysis of other causes of change in rabbit numbers. We calculated proportional survival as the ratio (number of rabbits present after RHD)/(number present before RHD), and used regression analysis to relate it to environmental and other variables. Proportional survival was lower at higher densities of rabbits; was lower if RHDV arrived naturally at the site rather than if it was deliberately released; was lower in areas with hot, dry climates than in areas with cold, wet climates; was lower in southern, inland areas than in warm, coastal areas; and, if the outbreak occurred during summer, was lower in areas of winter rainfall than in areas of summer rainfall. Rainfall seasonality was not correlated with survival at other times of the year. Only in the last effect was there a significant interaction with the time of the year that the outbreak occurred.Our statistical model describes correlations among the data, but does not in itself establish cause and effect. We interpret the properties of our statistical model to draw the following conclusions. First, the effectiveness of RHD is reduced in cold, wet areas and warm, coastal areas, because of the prevalence in these areas of one or more pre-existing caliciviruses in rabbits that impart year-round resistance to RHD. Second, we conclude that the poor summertime performance of RHD in areas that are wet in summer could result from poor survival of RHDV exposed to the combination of high temperature and high relative humidity, although it is also possible that during summer the effectiveness of vectors declines.

Coevolution of Host and Virus: Cellular Localization of Virus in Myxoma Virus Infection of Resistant and Susceptible European Rabbits

The coevolution of myxoma virus and the wild European rabbit in Australia and the development of resistance to myxomatosis in wild rabbits have been well described. However, the mechanism of resistance to myxomatosis in wild rabbits is not understood. To determine the basis of resistance, the pathogenesis of the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus were examined in Australian wild rabbits that have been naturally selected in the field for resistance to myxomatosis and in laboratory rabbits which have never been selected for resistance. Virus was localized in tissue sections by immunofluorescence. In all cases virus antigen was initally present in dendritic cells of the dermis before localizing predominantly to the epidermis by Day 6. Antigen-containing cells were detected in the lymph nodes by 24 h after inoculation. Virus replication occurred predominantly in T lymphocytes of the paracortex but SLS also replicated in germinal centers. SLS replication induced loss of most lymphocytes from the lymph nodes of susceptible rabbits. Apoptosis of lymphocytes within the lymph nodes was a major feature of all infections. These apoptotic cells did not contain detectable viral antigen but were often adjacent to infected cells. Ongoing apoptosis of lymphocytes within lymph nodes was also a feature of the recovery phase when very few or no virus-infected cells could be detected. Differences between virulent and attenuated viruses in the wild and laboratory rabbits were predominantly in the degree of tissue pathology in the draining lymph node and distal lymph node and in the type of inflammatory responses, particularly in the skin. SLS infection of laboratory rabbits was associated with a very mild inflammatory response, often distant from the site of virus replication and comprised predominantly of neutrophils. In contrast, Ur-infected rabbits and SLS-infected wild rabbits had an intense inflammatory response adjacent to the site of virus replication and this was comprised predominantly of mononuclear cells. Both the initial infection of dendritic cells and the ongoing destruction of lymphocytes provide obvious mechanisms for the suppression of the immune response by myxoma virus.

Use of ELISAs in field studies of rabbit haemorrhagic disease (RHD) in Australia

ELISA techniques developed for the veterinary diagnosis of Rabbit Haemorrhagic Disease (RHD) in domestic rabbits were used for studying the epidemiology of RHD in Australian wild rabbits. The combination of ELISA techniques that distinguished IgA, IgG and IgM antibody responses and a longitudinal data set, mainly based on capture-mark-recapture of rabbits, provided a reliable basis for interpreting serology and set the criteria used to classify rabbits' immunological status. Importantly, young with maternal antibodies, immune rabbits and rabbits apparently re-exposed to RHD were readily separated. Three outbreaks of RHD occurred in 1996-7. The timing of RHD outbreaks was mainly driven by recruitment of young rabbits that generally contracted RHD after they lost their maternally derived immunity. Young that lost maternal antibodies in summer were not immediately infected, apparently because transmission of RHDV slows at that time, but contracted RHD in the autumn when conditions were again suitable for disease spread.

The presence of cross-reactive antibodies to rabbit haemorrhagic disease virus in Australian wild rabbits prior to the escape of virus from quarantine.

Sera collected from Australian wild rabbits prior to the escape of rabbit haemorrhagic disease virus (RHDV) from Wardang Island were examined for RHDV antibodies using purified recombinant capsid protein VP60 expressed from baculovirus. A VP60-based indirect ELISA showed that 196 of 392 wild rabbit sera reacted (OD(450) >0.15) with VP60. Twenty sera (OD(450) ranging from 0.15-2.47), randomly chosen from the 196 positive sera, recognized the 64 kDa VP60 in Western blot analysis, indicating that the reactivity detected in ELISA is indeed specific to the VP60 antigen. In a separate study, sera of 23 rabbits from an RHD-free area after the escape of RHDV were tested by ELISA and 21 of the 23 rabbits were found to be positive. When these rabbits were challenged with a lethal dose of RHDV, 11 out of the 23 rabbits survived. The presence of RHDV-protective antibodies in some of these rabbits suggested that they had been exposed to a pre-existing non-virulent rabbit calicivirus closely related to RHDV. These results highlight the need to study the prevalence of, and to characterize, this viral agent in order to effectively control rabbit populations in Australia and New Zealand.

Adventures with poxviruses of vertebrates

Because they were the largest of all viruses and could be visualised with a light microscope, the poxviruses were the first viruses to be intensively studied in the laboratory. It was clear from an early date that they caused important diseases of humans and their domestic animals, such as smallpox, cowpox, camelpox, sheeppox, fowlpox and goatpox. This essay recounts some of the early history of their recognition and classification and then expands on aspects of research on poxviruses in which the author has been involved. Studies on the best-known genus, Orthopoxvirus, relate to the use of infectious ectromelia of mice as a model for smallpox, embracing both experimental epidemiology and pathogenesis, studies on the genetics of vaccinia virus and the problem of non-genetic reactivation (previously termed ‘transformation’) and the campaign for the global eradication of smallpox. The other group of poxviruses described here, the genus Leporipoxvirus, came to prominence when the myxoma virus was used for the biological control of Australian wild rabbits. This provided a unique natural experiment on the coevolution of a virus and its host. Future research will include further studies of the many immunomodulatory genes found in all poxviruses of vertebrates, since these provide clues about the workings of the immune system and how viruses have evolved to evade it. Some of the many recombinant poxvirus constructs currently being studied may come into use as vaccines or for immunocontraception. A field that warrants study but will probably remain neglected is the natural history of skunkpox, raccoonpox, taterapox, yabapox, tanapox and other little-known poxviruses. A dismal prospect is the possible use of smallpox virus for bioterrorism.