Viral biocontrol: grand experiments in disease emergence and evolution

Abstract

Although viral emergence is commonly associated with cross-species transmission, the processes and determinants of viral evolution in a novel host environment are poorly understood. We address key questions in virus emergence and evolution using data generated from two unique natural experiments: the deliberate release of myxoma virus (MYXV) and rabbit hemorrhagic disease virus (RHDV) as biological control (biocontrol) agents against the European rabbit in Australia, and which have been of enormous benefit to Australia's ecosystem and agricultural industries. Notably, although virulence evolution in MYXV and RHDV followed different trajectories, a strongly parallel evolutionary process was observed in Australia and Europe. These biocontrol agents were also characterized by a lack of transmission to nontarget host species, suggesting that there are major barriers to successful emergence.

Keywords: biocontrol; emergence; evolution; rabbit; virus.

Figure 1. Temporal impact of MYXV and RHDV on rabbit populations in Australia

The relative rabbit abundance in Australia since 1945. Rabbit population density is nominally set to 100% in 1945. The arrows indicate the timing of the release of MYXV in 1950 and RHDV in 1995. Adapted from [4].

Figure 2. Possible relationship between virulence and transmission in rabbit viruses

The x-axis depicts approximate host mortality rates (a measure of virulence) for the three rabbit viruses (colored accordingly) ranging from 0% (benign) to 100% (always lethal), including the different virulence grades of MYXV. The likely relationship between mortality and hypothetical values for viral titer (bars) and transmissibility (bell-shaped distributions) is also shown. Transmission via the fecal-oral route does not require host mortality so that RCV-A1 can evolve to low virulence. In contrast, RHDV can also be transmitted via flies that feed on animal carcasses, such that host death increases transmission rate. In the case of MYXV predominant mosquito and flea transmission occurs via diseased (live) animals, leading to a trade-off between virulence and transmission. Importantly, despite the markedly difference virulence levels in the three viruses, each can be considered as maximizing transmissibility.

Figure 3. Geographic structure of MYXV and RHDV in Australia

Time-scaled phylogenetic trees were estimated using the Bayesian Markov chain Monte Carlo method available in the BEAST package [81]. Both MYXV and RHDV analyses utilized the GTR+Γ model of nucleotide substitution, a relaxed molecular clock, and a constant population size coalescent prior. The MYXV data set comprised 25 complete genome sequences (alignment of 163,555 nt), while the RHDV data set comprised 51 capsid (VP60) sequences of 1,737 nt. The sequence names are colored according to the Australian state/territory from where they were isolated. The sequences in bold italics are the strains originally released in 1950 (MYXV) and 1995 (RHDV).

Figure 4. Parallel evolution of MYXV and RHDV on two continents

Schematic view of the evolutionary outcomes that followed the release of MYXV and RHDV in Australia (left) and Europe (right). Both viruses spread rapidly in both continents and are now endemic in the rabbit population. MYXV attenuated in Australia and Europe, whereas RHDV retained its high virulence in both locations. An increase in host resistance was observed for both viruses, although jumping to hosts other than lagomorphs has not been documented in Australia and Europe for either virus, although new RHDV strains are emerging in Europe. Rabbits facing right represent MYXV infection, whereas rabbits facing left denote RHDV infection.