Australia's biocontrol programs using Myxoma virus in 1950 and the Rabbit Calicivirus in 1995 have been extremely successful in drastically reducing pest rabbit numbers in Australia at a landscape scale. However, there is no status quo in rabbit biocontrol: the virus and rabbits constantly co-evolve, and changes in virus virulence and innate resistance in the host leads to rabbit numbers increasing yet again. We are continuing research to find new strategies that will help maintain benefits of biocontrol in the future.

A growing problem

By 1950 rabbit numbers in Australia reached 600 million.

Rabbits were introduced to Australia in 1859 by a wealthy Victorian grazier keen on the sport of hunting. After a fire destroyed the enclosures, rabbits started their campaign to conquer Australia. Within 70 years they spread to 70 per cent of Australia's landmass, the fastest known invasion by a mammal anywhere in the world. The damage caused by rabbits ranged from massive grazing pressure and competition with livestock to spreading weeds and accelerating erosion, and many farms were abandoned during the peak of the rabbit plaque.

Even today, with rabbit numbers still at a fraction of pre-Myxomatosis levels, rabbits cause an estimated AUD$200 million per year of economic damage, in addition to countless detrimental effects on biodiversity. Due to their selective grazing habits, less than one rabbit per hectare can completely prevent the regeneration of certain native tree and shrub species that are palatable to rabbits.

Biocontrol with viruses

CSIRO's predecessor, CSIR, carried out initial trials that ultimately resulted in the successful release of the Myxomatosis for the biological control of rabbits in 1950. As a result there was a dramatic reduction of Australia's rabbit population and AUD$68 million was recovered for our wool and meat industries within two years.

It was the world's first successful biological control program of a mammalian pest, taming a scourge that had threatened Australian agriculture and environment. However, by the late 1950s, host-pathogen co-evolution led to a less severe form of the disease, and rabbit numbers increased again, although not to pre-1950 levels.

In 1984 a new emerging disease of rabbits was described, Rabbit Haemorrhagic Disease Virus (RHDV), a calicivirus. The virus was brought to Australia in 1991 and was extensively assessed for its suitability as Australia's second rabbit biocontrol agent. After its escape from quarantine in 1995, it was officially released a year later. RHDV again reduced rabbit numbers to very low levels, with greatest impact in arid zones and lesser impact in high rainfall areas.

Further, scientists observed that RHDV was not as effective in cool, high rainfall areas and they suspected that a non-lethal calicivirus within the rabbits, closely related to RHDV, was to blame. This virus was identified by the CSIRO Rabbit Team in 2009, and it was shown that it can indeed partially and transiently protect rabbits from the lethal calicivirus RHDV, and thereby likely contributes to the lack of biocontrol success in the more temperate areas where the benign virus is present.

RHDV kept rabbit numbers low for over a decade and, in contrast to Myxomavirus, a reduction in virulence has so far not been observed. However, evidence for developing resistance in some Australian wild rabbit populations has now been described, and rabbit numbers are again on the rise.

A collaborative research project run by the Invasive Animals Cooperative Research Centre, led by the NSW Department of Primary Industries has evaluated overseas strains of RHDV for their ability to supplement Australia's existing biocontrol toolbox resulted in the nationwide release of an additional calicivirus strain in 2017. As part of this project the National Rabbit Biocontrol Monitoring Program was developed to help track the spread and record the effects of the K5 release, with the CSIRO Rabbit Team developing and implementing near real time diagnostic tests that enabled the project to monitor the spread and impact of the different types of virus in the landscape before, during and after the K5 release.

Through this work, Dr Strive's Team discovered the incursion of an additional, novel strain of calicivirus, termed RHDV2, which is able to overcome immune protection to older strains of RHDV and is also capable of lethally infecting European brown hares, which are also a recognised invasive pest in Australia. The Team played a leading role in tracking the spread of this virus across the continent and helped assess its impact on Australian rabbit populations. Within 18 months RHDV2 spread across the entire continent and became the dominant RHDV strain in Australia, leading to an estimated reduction of 60 per cent on average of wild rabbit populations.

In March 2019, the National Rabbit Biocontrol Monitoring Program implemented through CISS and with essential contributions from the CSIRO Rabbit Team received the Australian Government's Australian Biosecurity Award in the Industry category, which recognises significant outcomes for Australia's biosecurity system.

An ongoing battle

Some rabbits in cool, high-rainfall areas carry a benign virus that gives them partial immunity to the virulent calicivirus.

In 2007, Dr Tanja Strive's Team from CSIRO's Health & Biosecurity and through a project supported by the Invasive Animals CRC found that some rabbits in cool, high-rainfall areas carry a benign virus that gives them partial immunity to the virulent calicivirus.

The interaction between the rabbit host and its viruses forms a complex dynamic equilibrium, fine tuned to enable optimal spread of the virus without completely eliminating the host population, in a variety of environments. The examples of Myxoma virus and RHDV show that following the initial impact of a new biocontrol agent, rabbit numbers will likely bounce back again in the medium term following the intermediate relief that RHDV2 has provided.

This highlights the need to never solely rely on biological control to manage pest rabbits, but to always combine it with conventional control methods.

Nevertheless, biological control is by far the most cost effective large-scale control option, and keeping rabbit numbers low over long periods of time is essential for Australia's biodiversity and rural industries. Current research is therefore aiming at ways to help the virus stay ahead in the co-evolutionary arms race with its rabbit host, to protect the gains made by the past successful biocontrol initiatives and to keep rabbit numbers below the damage threshold.

CSIRO currently leads and participates in a series of collaborative projects run through the Centre for Invasive Species Solutions (CISS) investigating how the different caliciviruses in Australia can be applied in a more strategic manner to maximise the outcome of rabbit biocontrol operations and further reduce rabbit impacts to agriculture and environment. Through these projects, ongoing rabbit disease monitoring by CSIRO's team continues to provide critical data which is fed into a publicly available and continually updated rabbit calicivirus map of Australia, and provides information about which viruses are circulating, where they are circulating and when they are circulating. This map helps land managers in the development, coordination and timing of tailored rabbit management strategies, and aids veterinarians and pet rabbit owners in implementing biosecurity measures and, where available, vaccination strategies to protect non-target domestic rabbits.

A second line of research is investigating the development of a platform technology to accelerate and direct the natural evolution of the virus. The ultimate goal of this non-GMO approach is to repeatedly select tailored virus strains for subsequent virus releases, giving the virus the cutting edge to stay ahead in the co-evolutionary arms race with its host. To this end, the Team is investigating the use of rabbit organoid systems (3D cell culture systems that mimic miniature organs) for growing and studying rabbit caliciviruses in vivo.

Other lines of current research include searching for new and unrecognised viruses of rabbits and hares in Australia, that may be important as zoonotic pathogens (posing a risk to people), future potential biocontrol agents, or interfere with existing biocontrol viruses.

Novel emerging genetic technologies are opening up new opportunities for humane genetic biocontrol options, for example by skewing the sex ratio of pest animal populations that could lead to population crashes. While CSIRO is not currently pursuing this type of research for rabbits, this a fast moving field of science that may well provide exciting new opportunities for more humane landscape scale rabbit control in the future, provided safety and efficacy can be demonstrated.

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